Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Proteomics
  4. Fast Track Articles
  5. Fast Track Article
image of Decoding Glycobiomarkers in Non-Alcoholic Steatohepatitis (NASH) and Related Hepatocellular Carcinoma (HCC)

Abstract

The incidence of Hepatocellular carcinoma (HCC) is rising at an alarming rate. It is now the third leading cause of cancer deaths worldwide. Non-alcoholic fatty liver disease (NAFLD) and its more aggressive form of non-alcoholic steatohepatitis (NASH) are emerging as significant risk factors for liver cirrhosis and HCC. Post-translational modifications in proteins especially glycosylation leading to the synthesis of glycoproteins have been implicated in carcinogenesis. Dysregulated glycoproteins and aberrant glycosylation patterns might contribute to the establishment of a protumorogenic environment in NAFLD/NASH patients leading to the establishment of hepatocarcinogenesis. Understanding the molecular mechanisms underlying the changes in glycosylation patterns of certain proteins would help in deciphering the role of glycoproteins in liver cancer and develop novel prognostic and diagnostic markers and therapeutic strategies for the successful treatment of HCC. Herein we discuss some important glycoproteins and altered glycosylation patterns that can be employed as biomarkers for the early detection of HCC in NASH and NAFLD patients.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cp/10.2174/0115701646341608241025030547
2024-11-06
2025-01-18

  • From This Site

    /content/journals/cp/10.2174/0115701646341608241025030547
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  2. Brar G. Greten T.F. Graubard B.I. McNeel T.S. Petrick J.L. McGlynn K.A. Altekruse S.F. Hepatocellular carcinoma survival by etiology: A SEER‐medicare database analysis. Hepatol. Commun. 2020 4 10 1541 1551 10.1002/hep4.1564 33024922
    [Google Scholar]
  3. Reddy K.R. McLerran D. Marsh T. Parikh N. Roberts L.R. Schwartz M. Nguyen M.H. Befeler A. Page-Lester S. Tang R. Srivastava S. Rinaudo J.A. Feng Z. Marrero J.A. Incidence and risk factors for hepatocellular carcinoma in cirrhosis: The multicenter hepatocellular carcinoma early detection strategy (HEDS) study. Gastroenterology 2023 165 4 1053 1063.e6 10.1053/j.gastro.2023.06.027 37429366
    [Google Scholar]
  4. Zhang H. Spencer K. Burley S.K. Zheng X.F.S. Toward improving androgen receptor-targeted therapies in male-dominant hepatocellular carcinoma. Drug Discov. Today 2021 26 6 1539 1546 10.1016/j.drudis.2021.02.001 33561464
    [Google Scholar]
  5. Toh M.R. Wong E.Y.T. Wong S.H. Ng A.W.T. Loo L.H. Chow P.K.H. Ngeow J. Global epidemiology and genetics of hepatocellular carcinoma. Gastroenterology 2023 164 5 766 782 10.1053/j.gastro.2023.01.033 36738977
    [Google Scholar]
  6. Riazi K. Azhari H. Charette J.H. Underwood F.E. King J.A. Afshar E.E. Swain M.G. Congly S.E. Kaplan G.G. Shaheen A.A. The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 2022 7 9 851 861 10.1016/S2468‑1253(22)00165‑0 35798021
    [Google Scholar]
  7. Huang D.Q. El-Serag H.B. Loomba R. Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 2021 18 4 223 238 10.1038/s41575‑020‑00381‑6 33349658
    [Google Scholar]
  8. Bansal S. Vachher M. Arora T. Kumar B. Burman A. Visceral fat: A key mediator of NAFLD development and progression. Human Nutrition & Metabolism 2023 33 200210 10.1016/j.hnm.2023.200210
    [Google Scholar]
  9. Tan D.J.H. Ng C.H. Lin S.Y. Pan X.H. Tay P. Lim W.H. Teng M. Syn N. Lim G. Yong J.N. Quek J. Xiao J. Dan Y.Y. Siddiqui M.S. Sanyal A.J. Muthiah M.D. Loomba R. Huang D.Q. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis. Lancet Oncol. 2022 23 4 521 530 10.1016/S1470‑2045(22)00078‑X 35255263
    [Google Scholar]
  10. Yang J.D. Detect or not to detect very early stage hepatocellular carcinoma? The western perspective. Clin. Mol. Hepatol. 2019 25 4 335 343 10.3350/cmh.2019.0010 30924328
    [Google Scholar]
  11. Vachher M. Bansal S. Kumar B. Yadav S. Arora T. Wali N.M. Burman A. Contribution of organokines in the development of NAFLD/NASH associated hepatocellular carcinoma. J. Cell. Biochem. 2022 123 10 1553 1584 10.1002/jcb.30252 35818831
    [Google Scholar]
  12. Wang H. Yang L. Liu M. Luo J. Protein post-translational modifications in the regulation of cancer hallmarks. Cancer Gene Ther. 2023 30 4 529 547 10.1038/s41417‑022‑00464‑3 35393571
    [Google Scholar]
  13. Karlsson S. Nyström H. The extracellular matrix in colorectal cancer and its metastatic settling – Alterations and biological implications. Crit. Rev. Oncol. Hematol. 2022 175 103712 10.1016/j.critrevonc.2022.103712 35588938
    [Google Scholar]
  14. Vajaria B.N. Patel P.S. Glycosylation: A hallmark of cancer? Glycoconj. J. 2017 34 2 147 156 10.1007/s10719‑016‑9755‑2 27975160
    [Google Scholar]
  15. Reily C. Stewart T.J. Renfrow M.B. Novak J. Glycosylation in health and disease. Nat. Rev. Nephrol. 2019 15 6 346 366 10.1038/s41581‑019‑0129‑4 30858582
    [Google Scholar]
  16. Chen C. Ma B. Wang Y. Cui Q. Yao L. Li Y. Chen B. Feng Y. Tan Z. Structural insight into why S-linked glycosylation cannot adequately mimic the role of natural O-glycosylation. Int. J. Biol. Macromol. 2023 253 Pt 1 126649 10.1016/j.ijbiomac.2023.126649 37666405
    [Google Scholar]
  17. Loaeza-Reyes K.J. Zenteno E. Moreno-Rodríguez A. Torres-Rosas R. Argueta-Figueroa L. Salinas-Marín R. Castillo-Real L.M. Pina-Canseco S. Cervera Y.P. An overview of glycosylation and its impact on cardiovascular health and disease. Front. Mol. Biosci. 2021 8 751637 10.3389/fmolb.2021.751637 34869586
    [Google Scholar]
  18. van der Laarse S.A.M. Leney A.C. Heck A.J.R. Crosstalk between phosphorylation and O‐Glc NA cylation: Friend or foe. FEBS J. 2018 285 17 3152 3167 10.1111/febs.14491 29717537
    [Google Scholar]
  19. 4th ed Essentials of Glycobiology. Seeberger P.H. Cold Spring Harbor Laboratory Press Cold Spring Harbor, NY 2022
    [Google Scholar]
  20. Bloch J.S. John A. Mao R. Mukherjee S. Boilevin J. Irobalieva R.N. Darbre T. Scott N.E. Reymond J.L. Kossiakoff A.A. Goddard-Borger E.D. Locher K.P. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nat. Chem. Biol. 2023 19 5 575 584 10.1038/s41589‑022‑01219‑9 36604564
    [Google Scholar]
  21. Minakata S. Manabe S. Inai Y. Ikezaki M. Nishitsuji K. Ito Y. Ihara Y. Protein C-Mannosylation and C-Mannosyl Tryptophan in chemical biology and medicine. Molecules 2021 26 17 5258 10.3390/molecules26175258 34500691
    [Google Scholar]
  22. Buchowiecka A.K. Protein cysteine S-glycosylation: Oxidative hydrolysis of protein S-glycosidic bonds in aqueous alkaline environments. Amino Acids 2023 55 1 61 74 10.1007/s00726‑022‑03208‑7 36460841
    [Google Scholar]
  23. Fujita K. Hatano K. Hashimoto M. Tomiyama E. Miyoshi E. Nonomura N. Uemura H. Fucosylation in urological cancers. Int. J. Mol. Sci. 2021 22 24 13333 10.3390/ijms222413333 34948129
    [Google Scholar]
  24. Miyoshi E. Moriwaki K. Nakagawa T. Biological function of fucosylation in cancer biology. J. Biochem. 2007 143 6 725 729 10.1093/jb/mvn011 18218651
    [Google Scholar]
  25. Zhang Y. Wang R. Feng Y. Ma F. The role of sialyltransferases in gynecological malignant tumors. Life Sci. 2020 263 118670 10.1016/j.lfs.2020.118670 33121992
    [Google Scholar]
  26. Munkley J. Elliott D.J. Hallmarks of glycosylation in cancer. Oncotarget 2016 7 23 35478 35489 10.18632/oncotarget.8155 27007155
    [Google Scholar]
  27. Pinho S.S. Reis C.A. Glycosylation in cancer: Mechanisms and clinical implications. Nat. Rev. Cancer 2015 15 9 540 555 10.1038/nrc3982 26289314
    [Google Scholar]
  28. Matsumoto K. Yokote H. Arao T. Maegawa M. Tanaka K. Fujita Y. Shimizu C. Hanafusa T. Fujiwara Y. Nishio K. N ‐Glycan fucosylation of epidermal growth factor receptor modulates receptor activity and sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor. Cancer Sci. 2008 99 8 1611 1617 10.1111/j.1349‑7006.2008.00847.x 18754874
    [Google Scholar]
  29. Hashimoto S. Asao T. Takahashi J. Yagihashi Y. Nishimura T. Saniabadi A.R. Poland D.C.W. van Dijk W. Kuwano H. Kochibe N. Yazawa S. α 1 ‐Acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis. Cancer 2004 101 12 2825 2836 10.1002/cncr.20713 15536618
    [Google Scholar]
  30. Verhelst X. Dias A.M. Colombel J.F. Vermeire S. Van Vlierberghe H. Callewaert N. Pinho S.S. Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases. Gastroenterology 2020 158 1 95 110 10.1053/j.gastro.2019.08.060 31626754
    [Google Scholar]
  31. Wang Y. Chen H. Protein glycosylation alterations in hepatocellular carcinoma: Function and clinical implications. Oncogene 2023 42 24 1970 1979 10.1038/s41388‑023‑02702‑w 37193819
    [Google Scholar]
  32. Ramachandran P. Xu G. Huang H.H. Rice R. Zhou B. Lindpaintner K. Serie D. Serum glycoprotein markers in nonalcoholic steatohepatitis and hepatocellular carcinoma. J. Proteome Res. 2022 21 4 1083 1094 10.1021/acs.jproteome.1c00965 35286803
    [Google Scholar]
  33. Goldman R. Ressom H.W. Varghese R.S. Goldman L. Bascug G. Loffredo C.A. Abdel-Hamid M. Gouda I. Ezzat S. Kyselova Z. Mechref Y. Novotny M.V. Detection of hepatocellular carcinoma using glycomic analysis. Clin. Cancer Res. 2009 15 5 1808 1813 10.1158/1078‑0432.CCR‑07‑5261 19223512
    [Google Scholar]
  34. Mechref Y. Peng W. Gautam S. Ahmadi P. Lin Y. Zhu J. Zhang J. Liu S. Singal A.G. Parikh N.D. Lubman D.M. Mass spectrometry based biomarkers for early detection of HCC using a glycoproteomic approach. Adv. Cancer Res. 2023 157 23 56 10.1016/bs.acr.2022.07.005 36725111
    [Google Scholar]
  35. Blomme B. Van Steenkiste C. Callewaert N. Van Vlierberghe H. Alteration of protein glycosylation in liver diseases. J. Hepatol. 2009 50 3 592 603 10.1016/j.jhep.2008.12.010 19157620
    [Google Scholar]
  36. West C.A. Wang M. Herrera H. Liang H. Black A. Angel P.M. Drake R.R. Mehta A.S. N-linked glycan branching and fucosylation are increased directly in hcc tissue as determined through in situ glycan imaging. J. Proteome Res. 2018 17 10 3454 3462 10.1021/acs.jproteome.8b00323 30110170
    [Google Scholar]
  37. Burén S. Gomes A.L. Teijeiro A. Fawal M.A. Yilmaz M. Tummala K.S. Perez M. Rodriguez-Justo M. Campos-Olivas R. Megías D. Djouder N. Regulation of OGT by URI in response to glucose confers c-MYC-dependent survival mechanisms. Cancer Cell 2016 30 2 290 307 10.1016/j.ccell.2016.06.023 27505673
    [Google Scholar]
  38. Takayama H. Ohta M. Iwashita Y. Uchida H. Shitomi Y. Yada K. Inomata M. Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: A lectin microarray-based study. BMC Cancer 2020 20 1 192 10.1186/s12885‑020‑6699‑5 32143591
    [Google Scholar]
  39. Liu Y. Lan L. Li Y. Lu J. He L. Deng Y. Fei M. Lu J.W. Shangguan F. Lu J.P. Wang J. Wu L. Huang K. Lu B. N-glycosylation stabilizes MerTK and promotes hepatocellular carcinoma tumor growth. Redox Biol. 2022 54 102366 10.1016/j.redox.2022.102366 35728303
    [Google Scholar]
  40. Hu M. Zhang R. Yang J. Zhao C. Liu W. Huang Y. Lyu H. Xiao S. Guo D. Zhou C. Tang J. The role of N-glycosylation modification in the pathogenesis of liver cancer. Cell Death Dis. 2023 14 3 222 10.1038/s41419‑023‑05733‑z 36990999
    [Google Scholar]
  41. Chen C. Schmilovitz-Weiss H. Liu X. Pappo O. Halpern M. Sulkes J. Braun M. Cohen M. Barak N. Tur-Kaspa R. Vanhooren V. Van Vlierberghe H. Libert C. Contreras R. Ben-Ari Z. Serum protein N-glycans profiling for the discovery of potential biomarkers for nonalcoholic steatohepatitis. J. Proteome Res. 2009 8 2 463 470 10.1021/pr800656e 19140676
    [Google Scholar]
  42. Kamada Y. Akita M. Takeda Y. Yamada S. Fujii H. Sawai Y. Doi Y. Asazawa H. Nakayama K. Mizutani K. Fujii H. Yakushijin T. Miyazaki M. Ezaki H. Hiramatsu N. Yoshida Y. Kiso S. Imai Y. Kawada N. Takehara T. Miyoshi E. Serum fucosylated haptoglobin as a novel diagnostic biomarker for predicting hepatocyte ballooning and nonalcoholic steatohepatitis. PLoS One 2013 8 6 e66328 10.1371/journal.pone.0066328 23805214
    [Google Scholar]
  43. Mehta A. Block T.M. Fucosylated glycoproteins as markers of liver disease. Dis. Markers 2008 25 4-5 259 265 10.1155/2008/264594 19126969
    [Google Scholar]
  44. Wang Y. Fukuda T. Isaji T. Lu J. Loss of Al,6-Fucosyltransferase inhibits chemical-induced hepatocellular carcinoma and tumorigenesis by down-regulating several cell signaling pathways. FASEB J. 2015 29 3217 3227 10.1096/fj.15‑270710 25873065
    [Google Scholar]
  45. Kuo H.H. Lin R.J. Hung J.T. Hsieh C.B. Hung T.H. Lo F.Y. Ho M.Y. Yeh C.T. Huang Y.L. Yu J. Yu A.L. High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma. Sci. Rep. 2017 7 1 10750 10.1038/s41598‑017‑11136‑w 28883415
    [Google Scholar]
  46. Norton P.A. Mehta A.S. Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review. World J. Gastroenterol. 2019 25 23 2947 2960 10.3748/wjg.v25.i23.2947 31249452
    [Google Scholar]
  47. Nakagawa T. Uozumi N. Nakano M. Mizuno-Horikawa Y. Okuyama N. Taguchi T. Gu J. Kondo A. Taniguchi N. Miyoshi E. Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts. J. Biol. Chem. 2006 281 40 29797 29806 10.1074/jbc.M605697200 16899455
    [Google Scholar]
  48. Yang J.D. Dai J. Singal A.G. Gopal P. Addissie B.D. Nguyen M.H. Befeler A.S. Reddy K.R. Schwartz M. Harnois D.M. Yamada H. Gores G.J. Feng Z. Marrero J.A. Roberts L.R. Improved performance of serum alpha-fetoprotein for hepatocellular carcinoma diagnosis in HCV cirrhosis with normal alanine transaminase. Cancer Epidemiol. Biomarkers Prev. 2017 26 7 1085 1092 10.1158/1055‑9965.EPI‑16‑0747 28258053
    [Google Scholar]
  49. Marrero J.A. Kulik L.M. Sirlin C.B. Zhu A.X. Finn R.S. Abecassis M.M. Roberts L.R. Heimbach J.K. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice guidance by the American association for the study of liver diseases. Hepatology 2018 68 2 723 750 10.1002/hep.29913 29624699
    [Google Scholar]
  50. Sauzay C. Petit A. Bourgeois A.M. Barbare J.C. Chauffert B. Galmiche A. Houessinon A. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clin. Chim. Acta 2016 463 39 44 10.1016/j.cca.2016.10.006 27732875
    [Google Scholar]
  51. Wang X. Wang Q. Alpha-Fetoprotein and hepatocellular carcinoma immunity. Can. J. Gastroenterol. Hepatol. 2018 2018 1 8 10.1155/2018/9049252 29805966
    [Google Scholar]
  52. Tzartzeva K. Obi J. Rich N.E. Parikh N.D. Marrero J.A. Yopp A. Waljee A.K. Singal A.G. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: A meta-analysis. Gastroenterology 2018 154 6 1706 1718.e1 10.1053/j.gastro.2018.01.064 29425931
    [Google Scholar]
  53. Li D. Mallory T. Satomura S. AFP-L3: A new generation of tumor marker for hepatocellular carcinoma. Clin. Chim. Acta 2001 313 1-2 15 19 10.1016/S0009‑8981(01)00644‑1 11694234
    [Google Scholar]
  54. Choi J. Kim G.A. Han S. Lee W. Chun S. Lim Y.S. Longitudinal assessment of three serum biomarkers to detect very early‐stage hepatocellular carcinoma. Hepatology 2019 69 5 1983 1994 10.1002/hep.30233 30153338
    [Google Scholar]
  55. Nishizono I. Iida S. Suzuki N. Kawada H. Murakami H. Ashihara Y. Okada M. Rapid and sensitive chemiluminescent enzyme immunoassay for measuring tumor markers. Clin. Chem. 1991 37 9 1639 1644 10.1093/clinchem/37.9.1639 1716538
    [Google Scholar]
  56. Hanif H. Ali M.J. Susheela A.T. Khan I.W. Luna-Cuadros M.A. Khan M.M. Lau D.T.Y. Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma. World J. Gastroenterol. 2022 28 2 216 229 10.3748/wjg.v28.i2.216 35110946
    [Google Scholar]
  57. Ibrahim H.M. Elghannam M.Z. Elkhawaga O.A.Y. El-Sokkary A.M.A. Evaluation of serum alpha fetoprotein-L3 as an accuracy novel biomarker for the early diagnosis of hepatocellular carcinoma in Egyptian patients. Saudi J. Biol. Sci. 2021 28 10 5760 5764 10.1016/j.sjbs.2021.06.020 34588888
    [Google Scholar]
  58. Alsalloom A.A.M. An update of biochemical markers of hepatocellular carcinoma. Int. J. Health Sci. (Qassim) 2016 10 1 117 132 10.12816/0031219 27004063
    [Google Scholar]
  59. Bertino G. Ardiri A. Malaguarnera M. Malaguarnera G. Bertino N. Calvagno G.S. Hepatocellualar carcinoma serum markers. Semin. Oncol. 2012 39 4 410 433 10.1053/j.seminoncol.2012.05.001 22846859
    [Google Scholar]
  60. Taketa K. Sekiya C. Namiki M. Akamatsu K. Ohta Y. Endo Y. Kosaka K. Lectin-reactive profiles of alpha-fetoprotein characterizing hepatocellular carcinoma and related conditions. Gastroenterology 1990 99 2 508 518 10.1016/0016‑5085(90)91034‑4 1694805
    [Google Scholar]
  61. Zhou J.M. Wang T. Zhang K.H. AFP-L3 for the diagnosis of early hepatocellular carcinoma. Medicine (Baltimore) 2021 100 43 e27673 10.1097/MD.0000000000027673 34713864
    [Google Scholar]
  62. Babalı A. Çakal E. Purnak T. Bıyıkoğlu İ. Çakal B. Yüksel O. Köklü S. Serum α-fetoprotein levels in liver steatosis. Hepatol. Int. 2009 3 4 551 555 10.1007/s12072‑009‑9156‑8 19890679
    [Google Scholar]
  63. Best J. Bechmann L.P. Sowa J.P. Sydor S. Dechêne A. Pflanz K. Bedreli S. Schotten C. Geier A. Berg T. Fischer J. Vogel A. Bantel H. Weinmann A. Schattenberg J.M. Huber Y. Wege H. von Felden J. Schulze K. Bettinger D. Thimme R. Sinner F. Schütte K. Weiss K.H. Toyoda H. Yasuda S. Kumada T. Berhane S. Wichert M. Heider D. Gerken G. Johnson P. Canbay A. GALAD score detects early hepatocellular carcinoma in an international cohort of patients with nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol. 2020 18 3 728 735.e4 10.1016/j.cgh.2019.11.012 31712073
    [Google Scholar]
  64. Lim T.S. Rhee H. Kim G.M. Kim S.U. Kim B.K. Park J.Y. Ahn S.H. Han K.H. Choi J.Y. Kim D.Y. Alpha-Fetoprotein, Des-Gamma-Carboxy Prothrombin, and modified RECIST response as predictors of survival after transarterial radioembolization for hepatocellular carcinoma. J. Vasc. Interv. Radiol. 2019 30 8 1194 1200.e1 10.1016/j.jvir.2019.03.016 31235408
    [Google Scholar]
  65. Naraki T. Kohno N. Saito H. Fujimoto Y. Ohhira M. Morita T. Kohgo Y. γ-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-γ-carboxy prothrombin. Biochim. Biophys. Acta Mol. Basis Dis. 2002 1586 3 287 298 10.1016/S0925‑4439(01)00107‑7 11997080
    [Google Scholar]
  66. Wang S.B. Cheng Y.N. Cui S.X. Zhong J.L. Ward S.G. Sun L.R. Chen M.H. Kokudo N. Tang W. Qu X.J. Des-γ-carboxy prothrombin stimulates human vascular endothelial cell growth and migration. Clin. Exp. Metastasis 2009 26 5 469 477 10.1007/s10585‑009‑9246‑y 19263229
    [Google Scholar]
  67. Zhang Y.S. Chu J.H. Cui S.X. Song Z.Y. Qu X.J. Des-γ-carboxy prothrombin (DCP) as a potential autologous growth factor for the development of hepatocellular carcinoma. Cell. Physiol. Biochem. 2014 34 3 903 915 10.1159/000366308 25200250
    [Google Scholar]
  68. Yuen M.F. Lai C.L. Serological markers of liver cancer. Best Pract. Res. Clin. Gastroenterol. 2005 19 1 91 99 10.1016/j.bpg.2004.10.003 15757806
    [Google Scholar]
  69. Pan Y. Chen H. Yu J. Biomarkers in hepatocellular carcinoma: Current status and future perspectives. Biomedicines 2020 8 12 576 10.3390/biomedicines8120576 33297335
    [Google Scholar]
  70. Nakamura S. Nouso K. Sakaguchi K. Ito Y.M. Ohashi Y. Kobayashi Y. Toshikuni N. Tanaka H. Miyake Y. Matsumoto E. Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am. J. Gastroenterol. 2006 101 9 2038 2043 10.1111/j.1572‑0241.2006.00681.x 16848811
    [Google Scholar]
  71. Li H. Liu H. Yan L.J. Ding Z.N. Zhang X. Pan G.Q. Han C.L. Tian B.W. Tan S.Y. Dong Z.R. Wang D.X. Yan Y.C. Li T. Performance of GALAD score and serum biomarkers for detecting NAFLD-related HCC: A systematic review and network meta-analysis. Expert Rev. Gastroenterol. Hepatol. 2023 17 11 1159 1167 10.1080/17474124.2023.2279175 37929312
    [Google Scholar]
  72. Dobryszycka W. Biological functions of haptoglobin--new pieces to an old puzzle. Eur. J. Clin. Chem. Clin. Biochem. 1997 35 9 647 654 9352226
    [Google Scholar]
  73. Zhang S. Shang S. Li W. Qin X. Liu Y. Insights on N-glycosylation of human haptoglobin and its association with cancers. Glycobiology 2016 26 7 684 692 10.1093/glycob/cww016 26873173
    [Google Scholar]
  74. Hülsmeier A.J. Tobler M. Burda P. Hennet T. Glycosylation site occupancy in health, congenital disorder of glycosylation and fatty liver disease. Sci. Rep. 2016 6 1 33927 10.1038/srep33927 27725718
    [Google Scholar]
  75. Nakagawa T. Muramoto Y. Hori M. Mihara S. Marubayashi T. Nakagawa K. A preliminary investigation of the association between haptoglobin polymorphism, serum ferritin concentration and fatty liver disease. Clin. Chim. Acta 2008 398 1-2 34 38 10.1016/j.cca.2008.08.004 18760271
    [Google Scholar]
  76. Banini B.A. Cazanave S.C. Yates K.P. Asgharpour A. Vincent R. Mirshahi F. Le P. Contos M.J. Tonascia J. Chalasani N.P. Kowdley K.V. McCullough A.J. Behling C.A. Schwimmer J.B. Lavine J.E. Sanyal A.J. Haptoglobin 2 allele is associated with histologic response to vitamin E in subjects with nonalcoholic steatohepatitis. J. Clin. Gastroenterol. 2019 53 10 750 758 10.1097/MCG.0000000000001142 30586008
    [Google Scholar]
  77. Naryzny S.N. Legina O.K. Haptoglobin as a biomarker. Biochem. Suppl. Ser. B: Biomed. Chem. 2021 15 3 184 198 10.1134/S1990750821030069 34422226
    [Google Scholar]
  78. Narisada M. Kawamoto S. Kuwamoto K. Moriwaki K. Nakagawa T. Matsumoto H. Asahi M. Koyama N. Miyoshi E. Identification of an inducible factor secreted by pancreatic cancer cell lines that stimulates the production of fucosylated haptoglobin in hepatoma cells. Biochem. Biophys. Res. Commun. 2008 377 3 792 796 10.1016/j.bbrc.2008.10.061 18951869
    [Google Scholar]
  79. Zhu J. Huang J. Zhang J. Chen Z. Lin Y. Grigorean G. Li L. Liu S. Singal A.G. Parikh N.D. Lubman D.M. Glycopeptide biomarkers in serum haptoglobin for hepatocellular carcinoma detection in patients with nonalcoholic steatohepatitis. J. Proteome Res. 2020 19 8 3452 3466 10.1021/acs.jproteome.0c00270 32412768
    [Google Scholar]
  80. Shang S. Li W. Qin X. Zhang S. Liu Y. Aided diagnosis of hepatocellular carcinoma using serum fucosylated haptoglobin ratios. J. Cancer 2017 8 5 887 893 10.7150/jca.17747 28382152
    [Google Scholar]
  81. Lin Y. Zhu J. Zhang J. Dai J. Liu S. Arroyo A. Rose M. Singal A.G. Parikh N.D. Lubman D.M. Glycopeptides with sialyl lewis antigen in serum haptoglobin as candidate biomarkers for nonalcoholic steatohepatitis hepatocellular carcinoma using a higher-energy collision-induced dissociation parallel reaction monitoring-mass spectrometry method. ACS Omega 2022 7 26 22850 22860 10.1021/acsomega.2c02600 35811936
    [Google Scholar]
  82. Ang I.L. Poon T.C.W. Lai P.B.S. Chan A.T.C. Ngai S.M. Hui A.Y. Johnson P.J. Sung J.J.Y. Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: A glycoproteomic approach. J. Proteome Res. 2006 5 10 2691 2700 10.1021/pr060109r 17022640
    [Google Scholar]
  83. Zhu J. Lin Z. Wu J. Yin H. Dai J. Feng Z. Marrero J. Lubman D.M. Analysis of serum haptoglobin fucosylation in hepatocellular carcinoma and liver cirrhosis of different etiologies. J. Proteome Res. 2014 13 6 2986 2997 10.1021/pr500128t 24807840
    [Google Scholar]
  84. Gutierrez Reyes C.D. Huang Y. Atashi M. Zhang J. Zhu J. Liu S. Parikh N.D. Singal A.G. Dai J. Lubman D.M. Mechref Y. PRM-MS quantitative analysis of isomeric N-Glycopeptides derived from human serum haptoglobin of patients with cirrhosis and hepatocellular carcinoma. Metabolites 2021 11 8 563 10.3390/metabo11080563 34436504
    [Google Scholar]
  85. Asazawa H. Kamada Y. Takeda Y. Takamatsu S. Shinzaki S. Kim Y. Nezu R. Kuzushita N. Mita E. Kato M. Miyoshi E. Serum fucosylated haptoglobin in chronic liver diseases as a potential biomarker of hepatocellular carcinoma development. Clin Chem Lab Med. 2015 53 1 95 102 10.1515/cclm‑2014‑0427 25060348
    [Google Scholar]
  86. Peta V. Zhu J. Lubman D.M. Huguet S. Imbert-Bismutd F. Bolbach G. Clodic G. Matheron L. Ngo Y. Raluca P. Housset C. Rezai K. Poynard T. Input of serum haptoglobin fucosylation profile in the diagnosis of hepatocellular carcinoma in patients with non-cirrhotic liver disease. Clin. Res. Hepatol. Gastroenterol. 2020 44 5 681 691 10.1016/j.clinre.2019.12.010 31964615
    [Google Scholar]
  87. Zhang Y. Zhu J. Yin H. Marrero J. Zhang X.X. Lubman D.M. ESI–LC–MS method for haptoglobin fucosylation analysis in hepatocellular carcinoma and liver cirrhosis. J. Proteome Res. 2015 14 12 5388 5395 10.1021/acs.jproteome.5b00792 26503433
    [Google Scholar]
  88. Shirai K. Hikita H. Sakamori R. Doi A. Tahata Y. Sakane S. Kamada Y. Murai K. Nishio A. Yamada R. Kodama T. Nozaki Y. Kakita N. Ishida H. Nakanishi F. Morishita N. Imanaka K. Sakakibara M. Tatsumi T. Miyoshi E. Takehara T. Fucosylated haptoglobin is a novel predictive marker of hepatocellular carcinoma after hepatitis C virus elimination in patients with advanced liver fibrosis. PLoS One 2022 17 12 e0279416 10.1371/journal.pone.0279416 36542633
    [Google Scholar]
  89. Kohansal-Nodehi M. Swiatek-de Lange M. Kroeniger K. Rolny V. Tabarés G. Piratvisuth T. Tanwandee T. Thongsawat S. Sukeepaisarnjaroen W. Esteban J.I. Bes M. Köhler B. Chan H.L.Y. Busskamp H. Discovery of a haptoglobin glycopeptides biomarker panel for early diagnosis of hepatocellular carcinoma. Front. Oncol. 2023 13 1213898 10.3389/fonc.2023.1213898 37920152
    [Google Scholar]
  90. Tripodi A. Lombardi R. Primignani M. La Mura V. Peyvandi F. Fracanzani A.L. Hypercoagulability in patients with non-alcoholic fatty liver disease (NAFLD): Causes and consequences. Biomedicines 2022 10 2 249 10.3390/biomedicines10020249 35203457
    [Google Scholar]
  91. Wang J. Wang X. Lin S. Chen C. Wang C. Ma Q. Jiang B. Identification of kininogen-1 as a serum biomarker for the early detection of advanced colorectal adenoma and colorectal cancer. PLoS One 2013 8 7 e70519 10.1371/journal.pone.0070519 23894665
    [Google Scholar]
  92. Abdul-Rahman P.S. Lim B.K. Hashim O.H. Expression of high‐abundance proteins in sera of patients with endometrial and cervical cancers: Analysis using 2‐DE with silver staining and lectin detection methods. Electrophoresis 2007 28 12 1989 1996 10.1002/elps.200600629 17503403
    [Google Scholar]
  93. Doustjalali S.R. Yusof R. Yip C.H. Looi L.M. Pillay B. Hashim O.H. Aberrant expression of acute‐phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors. Electrophoresis 2004 25 14 2392 2401 10.1002/elps.200305950 15274022
    [Google Scholar]
  94. Xu J. Fang J. Cheng Z. Fan L. Hu W. Zhou F. Shen H. Overexpression of the Kininogen-1 inhibits proliferation and induces apoptosis of glioma cells. J. Exp. Clin. Cancer Res. 2018 37 1 180 10.1186/s13046‑018‑0833‑0 30068373
    [Google Scholar]
  95. Liu W. Liu B. Cai Q. Li J. Chen X. Zhu Z. Proteomic identification of serum biomarkers for gastric cancer using multi-dimensional liquid chromatography and 2D differential gel electrophoresis. Clin. Chim. Acta 2012 413 13-14 1098 1106 10.1016/j.cca.2012.03.003 22446497
    [Google Scholar]
  96. Quesada-Calvo F. Massot C. Bertrand V. Longuespée R. Blétard N. Somja J. Mazzucchelli G. Smargiasso N. Baiwir D. De Pauw-Gillet M.C. Delvenne P. Malaise M. Coimbra Marques C. Polus M. De Pauw E. Meuwis M.A. Louis E. OLFM4, KNG1 and Sec24C identified by proteomics and immunohistochemistry as potential markers of early colorectal cancer stages. Clin. Proteomics 2017 14 1 9 10.1186/s12014‑017‑9143‑3 28344541
    [Google Scholar]
  97. Wang M. Long R.E. Comunale M.A. Junaidi O. Marrero J. Di Bisceglie A.M. Block T.M. Mehta A.S. Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev. 2009 18 6 1914 1921 10.1158/1055‑9965.EPI‑08‑0980 19454616
    [Google Scholar]
  98. Wang M. Sanda M. Comunale M.A. Herrera H. Swindell C. Kono Y. Singal A.G. Marrero J. Block T. Goldman R. Mehta A. Changes in the glycosylation of kininogen and the development of a kininogen-based algorithm for the early detection of HCC. Cancer Epidemiol. Biomarkers Prev. 2017 26 5 795 803 10.1158/1055‑9965.EPI‑16‑0974 28223431
    [Google Scholar]
  99. Wang M. Shen J. Herrera H. Singal A. Swindell C. Renquan L. Mehta A. Biomarker analysis of fucosylated kininogen through depletion of lectin reactive heterophilic antibodies in hepatocellular carcinoma. J. Immunol. Methods 2018 462 59 64 10.1016/j.jim.2018.08.010 30144410
    [Google Scholar]
  100. Wang M. Singal A.G. Parikh N. Kono Y. Marrero J. Mehta A. A biomarker panel based upon AFP, fucosylated kininogen and PEG-precipitated IgG is highly accurate for the early detection hepatocellular carcinoma in patients with cirrhosis in phase II and phase III biomarker evaluation. Cancers (Basel) 2022 14 23 5970 10.3390/cancers14235970 36497452
    [Google Scholar]
  101. Greene C.M. Marciniak S.J. Teckman J. Ferrarotti I. Brantly M.L. Lomas D.A. Stoller J.K. McElvaney N.G. α1-Antitrypsin deficiency. Nat. Rev. Dis. Primers 2016 2 1 16051 10.1038/nrdp.2016.51 27465791
    [Google Scholar]
  102. Comunale M.A. Rodemich-Betesh L. Hafner J. Wang M. Norton P. Di Bisceglie A.M. Block T. Mehta A. Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: Implications for a biomarker of hepatocellular carcinoma. PLoS One 2010 5 8 e12419 10.1371/journal.pone.0012419 20811639
    [Google Scholar]
  103. Kobayashi T. Ogawa K. Furukawa J. Hanamatsu H. Hato M. Yoshinaga T. Morikawa K. Suda G. Sho T. Nakai M. Higashino K. Numata Y. Shinohara Y. Sakamoto N. Quantifying protein-specific N-glycome profiles by focused protein and immunoprecipitation glycomics. J. Proteome Res. 2019 18 8 3133 3141 10.1021/acs.jproteome.9b00232 31266306
    [Google Scholar]
  104. Ogawa K. Kobayashi T. Furukawa J. Hanamatsu H. Nakamura A. Suzuki K. Kawagishi N. Ohara M. Umemura M. Nakai M. Sho T. Suda G. Morikawa K. Baba M. Furuya K. Terashita K. Kobayashi T. Onodera M. Horimoto T. Shinada K. Tsunematsu S. Tsunematsu I. Meguro T. Mitsuhashi T. Hato M. Higashino K. Shinohara Y. Sakamoto N. Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: A novel glycobiomarker for non-alcoholic steatohepatitis. Sci. Rep. 2020 10 1 321 10.1038/s41598‑019‑56947‑1 31941930
    [Google Scholar]
  105. Abbas S.H. Pickett E. Lomas D.A. Thorburn D. Gooptu B. Hurst J.R. Marshall A. Non-invasive testing for liver pathology in alpha-1 antitrypsin deficiency. BMJ Open Respir. Res. 2020 7 1 e000820 10.1136/bmjresp‑2020‑000820 33323365
    [Google Scholar]
  106. Yin H. Zhu J. Wang M. Yao Z.P. Lubman D.M. Quantitative Analysis of α-1-Antitrypsin Glycosylation Isoforms in HCC Patients Using LC-HCD-PRM-MS. Anal. Chem. 2020 92 12 8201 8208 10.1021/acs.analchem.0c00420 32426967
    [Google Scholar]
  107. Bergin D.A. Reeves E.P. Meleady P. Henry M. McElvaney O.J. Carroll T.P. Condron C. Chotirmall S.H. Clynes M. O’Neill S.J. McElvaney N.G. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J. Clin. Invest. 2010 120 12 4236 4250 10.1172/JCI41196 21060150
    [Google Scholar]
  108. O’Brien M.E. Fee L. Browne N. Carroll T.P. Meleady P. Henry M. McQuillan K. Murphy M.P. Logan M. McCarthy C. McElvaney O.J. Reeves E.P. McElvaney N.G. Activation of complement component 3 is associated with airways disease and pulmonary emphysema in alpha-1 antitrypsin deficiency. Thorax 2020 75 4 321 330 10.1136/thoraxjnl‑2019‑214076 31959730
    [Google Scholar]
  109. Janciauskiene S. Wrenger S. Immenschuh S. Olejnicka B. Greulich T. Welte T. Chorostowska-Wynimko J. The multifaceted effects of Alpha1-antitrypsin on neutrophil functions. Front. Pharmacol. 2018 9 341 10.3389/fphar.2018.00341 29719508
    [Google Scholar]
  110. Ercetin E. Richtmann S. Delgado B.M. Gomez-Mariano G. Wrenger S. Korenbaum E. Liu B. DeLuca D. Kühnel M.P. Jonigk D. Yuskaeva K. Warth A. Muley T. Winter H. Meister M. Welte T. Janciauskiene S. Schneider M.A. Clinical significance of SERPINA1 gene and its encoded Alpha1-antitrypsin protein in NSCLC. Cancers (Basel) 2019 11 9 1306 10.3390/cancers11091306 31487965
    [Google Scholar]
  111. Koukoulis G.K. Shen J. Virtanen I. Gould V.E. Vitronectin in the cirrhotic liver: An immunomarker of mature fibrosis. Hum. Pathol. 2001 32 12 1356 1362 10.1053/hupa.2001.29675 11774169
    [Google Scholar]
  112. Hayashida M. Hashimoto K. Ishikawa T. Miyamoto Y. Vitronectin deficiency attenuates hepatic fibrosis in a non‐alcoholic steatohepatitis‐induced mouse model. Int. J. Exp. Pathol. 2019 100 2 72 82 10.1111/iep.12306 30887659
    [Google Scholar]
  113. Lin Y. Zhu J. Pan L. Zhang J. Tan Z. Olivares J. Singal A.G. Parikh N.D. Lubman D.M. A panel of glycopeptides as candidate biomarkers for early diagnosis of NASH hepatocellular carcinoma using a stepped HCD method and prm evaluation. J. Proteome Res. 2021 20 6 3278 3289 10.1021/acs.jproteome.1c00175 33929864
    [Google Scholar]
  114. Hwang H. Lee J.Y. Lee H.K. Park G.W. Jeong H.K. Moon M.H. Kim J.Y. Yoo J.S. In-depth analysis of site-specific N-glycosylation in vitronectin from human plasma by tandem mass spectrometry with immunoprecipitation. Anal. Bioanal. Chem. 2014 406 30 7999 8011 10.1007/s00216‑014‑8226‑5 25374123
    [Google Scholar]
  115. Schvartz I. Seger D. Shaltiel S. Vitronectin. Int. J. Biochem. Cell Biol. 1999 31 5 539 544 10.1016/S1357‑2725(99)00005‑9 10399314
    [Google Scholar]
  116. Montaldo C. Mattei S. Baiocchini A. Rotiroti N. Nonno F.D. Pucillo L.P. Cozzolino A.M. Battistelli C. Amicone L. Ippolito G. van Noort V. Conigliaro A. Alonzi T. Tripodi M. Mancone C. Spike‐in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload. Proteomics 2014 14 9 1107 1115 10.1002/pmic.201300422 24616218
    [Google Scholar]
  117. Edwards S. Lalor P.F. Tuncer C. Adams D.H. Vitronectin in human hepatic tumours contributes to the recruitment of lymphocytes in an αvβ3-independent manner. Br. J. Cancer 2006 95 11 1545 1554 10.1038/sj.bjc.6603467 17088900
    [Google Scholar]
  118. Vitronectin (VTN): A novel diagnostic and prognostic marker for Hepatocellular Carcinoma (HCC) on top of chronic hepatitis C virus related diseases. Egypt. J. Hosp. Med. 2023 92 1 6363 6370 10.21608/ejhm.2023.314498
    [Google Scholar]
  119. Del Ben M. Overi D. Polimeni L. Carpino G. Labbadia G. Baratta F. Pastori D. Noce V. Gaudio E. Angelico F. Mancone C. Overexpression of the vitronectin V10 subunit in patients with nonalcoholic steatohepatitis: Implications for noninvasive diagnosis of NASH. Int. J. Mol. Sci. 2018 19 2 603 10.3390/ijms19020603 29463024
    [Google Scholar]
  120. Rangaswami H. Bulbule A. Kundu G.C. Osteopontin: Role in cell signaling and cancer progression. Trends Cell Biol. 2006 16 2 79 87 10.1016/j.tcb.2005.12.005 16406521
    [Google Scholar]
  121. Wu Q. Li L. Miao C. Hasnat M. Sun L. Jiang Z. Zhang L. Osteopontin promotes hepatocellular carcinoma progression through inducing JAK2/STAT3/NOX1-mediated ROS production. Cell Death Dis. 2022 13 4 341 10.1038/s41419‑022‑04806‑9 35418176
    [Google Scholar]
  122. Nomiyama T. Perez-Tilve D. Ogawa D. Gizard F. Zhao Y. Heywood E.B. Jones K.L. Kawamori R. Cassis L.A. Tschöp M.H. Bruemmer D. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J. Clin. Invest. 2007 117 10 2877 2888 10.1172/JCI31986 17823662
    [Google Scholar]
  123. Kahles F. Findeisen H.M. Bruemmer D. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Mol. Metab. 2014 3 4 384 393 10.1016/j.molmet.2014.03.004 24944898
    [Google Scholar]
  124. Kiefer F.W. Zeyda M. Gollinger K. Pfau B. Neuhofer A. Weichhart T. Säemann M.D. Geyeregger R. Schlederer M. Kenner L. Stulnig T.M. Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 2010 59 4 935 946 10.2337/db09‑0404 20107108
    [Google Scholar]
  125. Icer M.A. Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin. Clin. Biochem. 2018 59 17 24 10.1016/j.clinbiochem.2018.07.003 30003880
    [Google Scholar]
  126. Glass O. Henao R. Patel K. Guy C.D. Gruss H.J. Syn W.K. Moylan C.A. Streilein R. Hall R. Mae Diehl A. Abdelmalek M.F. Serum interleukin‐8, osteopontin, and monocyte chemoattractant protein 1 are associated with hepatic fibrosis in patients with nonalcoholic fatty liver disease. Hepatol. Commun. 2018 2 11 1344 1355 10.1002/hep4.1237 30411081
    [Google Scholar]
  127. Nardo A.D. Grün N.G. Zeyda M. Dumanic M. Oberhuber G. Rivelles E. Helbich T.H. Markgraf D.F. Roden M. Claudel T. Trauner M. Stulnig T.M. Impact of osteopontin on the development of non‐alcoholic liver disease and related hepatocellular carcinoma. Liver Int. 2020 40 7 1620 1633 10.1111/liv.14464 32281248
    [Google Scholar]
  128. Shang S. Plymoth A. Ge S. Feng Z. Rosen H.R. Sangrajrang S. Hainaut P. Marrero J.A. Beretta L. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2012 55 2 483 490 10.1002/hep.24703 21953299
    [Google Scholar]
  129. Sun H.Y. Li Y. Guo K. Kang X.N. Sun C. Liu Y.K. Identification of metastasis-related osteopontin expression and glycosylation in hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 2011 19 12 904 907 22525502
    [Google Scholar]
  130. Bruha R. Vitek L. Smid V. Osteopontin – A potential biomarker of advanced liver disease. Ann. Hepatol. 2020 19 4 344 352 10.1016/j.aohep.2020.01.001 32005637
    [Google Scholar]
  131. Sun T. Li P. Sun D. Bu Q. Li G. Prognostic value of osteopontin in patients with hepatocellular carcinoma. Medicine (Baltimore) 2018 97 43 e12954 10.1097/MD.0000000000012954 30412113
    [Google Scholar]
  132. Zhou F. Shang W. Yu X. Tian J. Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med. Res. Rev. 2018 38 2 741 767 10.1002/med.21455 28621802
    [Google Scholar]
  133. Capurro M. Wanless I.R. Sherman M. Deboer G. Shi W. Miyoshi E. Filmus J. Glypican-3: A novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 2003 125 1 89 97 10.1016/S0016‑5085(03)00689‑9 12851874
    [Google Scholar]
  134. Ismail M. Glypican-3-expressing hepatocellular carcinoma in a non-cirrhotic patient with nonalcoholic steatohepatitis: Case report and literature review. Gastroenterol. Res. 2010 3 5 223 228 10.4021/gr224w 27957002
    [Google Scholar]
  135. Nakatsura T. Yoshitake Y. Senju S. Monji M. Komori H. Motomura Y. Hosaka S. Beppu T. Ishiko T. Kamohara H. Ashihara H. Katagiri T. Furukawa Y. Fujiyama S. Ogawa M. Nakamura Y. Nishimura Y. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem. Biophys. Res. Commun. 2003 306 1 16 25 10.1016/S0006‑291X(03)00908‑2 12788060
    [Google Scholar]
  136. Chen M. Li G. Yan J. Lu X. Cui J. Ni Z. Cheng W. Qian G. Zhang J. Tu H. Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma. Clin. Chim. Acta 2013 423 105 111 10.1016/j.cca.2013.04.026 23643963
    [Google Scholar]
  137. Haruyama Y. Kataoka H. Glypican-3 is a prognostic factor and an immunotherapeutic target in hepatocellular carcinoma. World J. Gastroenterol. 2016 22 1 275 283 10.3748/wjg.v22.i1.275 26755876
    [Google Scholar]
  138. Guo M. Zhang H. Zheng J. Liu Y. Glypican-3: A new target for diagnosis and treatment of hepatocellular carcinoma. J. Cancer 2020 11 8 2008 2021 10.7150/jca.39972 32127929
    [Google Scholar]
  139. Janiszewska E. Kmieciak A. Kacperczyk M. Witkowska A. Kratz E.M. The influence of clusterin glycosylation variability on selected pathophysiological processes in the human body. Oxid. Med. Cell. Longev. 2022 2022 1 25 10.1155/2022/7657876 36071866
    [Google Scholar]
  140. Mamun M.A.A. Zheng Y.C. Wang N. Wang B. Zhang Y. Pang J.R. Shen D.D. Liu H.M. Gao Y. Decoding CLU (Clusterin): Conquering cancer treatment resistance and immunological barriers. Int. Immunopharmacol. 2024 137 112355 10.1016/j.intimp.2024.112355 38851158
    [Google Scholar]
  141. Won J.C. Park C.Y. Oh S.W. Lee E.S. Youn B.S. Kim M.S. Plasma clusterin (ApoJ) levels are associated with adiposity and systemic inflammation. PLoS One 2014 9 7 e103351 10.1371/journal.pone.0103351 25076422
    [Google Scholar]
  142. Wang Y. Shen Y. Hu T. Wang Y. Ma X. Yu H. Bao Y. Associations between serum clusterin levels and non-alcoholic fatty liver disease. Endocr. Connect. 2023 12 7 e220545 10.1530/EC‑22‑0545 37043769
    [Google Scholar]
  143. Seo H.Y. Kim M.K. Jung Y.A. Jang B.K. Yoo E.K. Park K.G. Lee I.K. Clusterin decreases hepatic SREBP-1c expression and lipid accumulation. Endocrinology 2013 154 5 1722 1730 10.1210/en.2012‑2009 23515283
    [Google Scholar]
  144. Kwon M.J. Ju T. Heo J.Y. Kim Y.W. Kim J.Y. Won K.C. Kim J.R. Bae Y.K. Park I.S. Min B.H. Lee I.K. Park S.Y. Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice. Endocrinology 2014 155 6 2089 2101 10.1210/en.2013‑1870 24684302
    [Google Scholar]
  145. Park J.S. Shim Y.J. Kang B.H. Lee W.K. Min B.H. Hepatocyte-specific clusterin overexpression attenuates diet-induced nonalcoholic steatohepatitis. Biochem. Biophys. Res. Commun. 2018 495 2 1775 1781 10.1016/j.bbrc.2017.12.045 29229391
    [Google Scholar]
  146. Park J.S. Lee W.K. Kim H.S. Seo J.A. Kim D.H. Han H.C. Min B.H. Clusterin overexpression protects against western diet-induced obesity and NAFLD. Sci. Rep. 2020 10 1 17484 10.1038/s41598‑020‑73927‑y 33060605
    [Google Scholar]
  147. Stefan N. Schick F. Birkenfeld A.L. Häring H.U. White M.F. The role of hepatokines in NAFLD. Cell Metab. 2023 35 2 236 252 10.1016/j.cmet.2023.01.006 36754018
    [Google Scholar]
  148. Kang Y.K. Hong S.W. Lee H. Kim W.H. Overexpression of clusterin in human hepatocellular carcinoma. Hum. Pathol. 2004 35 11 1340 1346 10.1016/j.humpath.2004.07.021 15668890
    [Google Scholar]
  149. Lau S.H. Sham J.S.T. Xie D. Tzang C-H. Tang D. Ma N. Hu L. Wang Y. Wen J-M. Xiao G. Zhang W-M. Lau G.K.K. Yang M. Guan X-Y. Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene 2006 25 8 1242 1250 10.1038/sj.onc.1209141 16247463
    [Google Scholar]
  150. Peng M. Deng J. Zhou S. Tao T. Su Q. Xue Y. Yang X. The role of Clusterin in cancer metastasis. Cancer Manag. Res. 2019 11 2405 2414 10.2147/CMAR.S196273 31114318
    [Google Scholar]
  151. Comunale M.A. Wang M. Rodemich-Betesh L. Hafner J. Lamontagne A. Klein A. Marrero J. Di Bisceglie A.M. Gish R. Block T. Mehta A. Novel changes in glycosylation of serum Apo-J in patients with hepatocellular carcinoma. Cancer Epidemiol. Biomarkers Prev. 2011 20 6 1222 1229 10.1158/1055‑9965.EPI‑10‑1047 21467232
    [Google Scholar]
  152. Gao G. Luan X. Diagnostic performance of clusterin in hepatocellular carcinoma: A meta-analysis. Int. J. Biol. Markers 2022 37 4 404 411 10.1177/03936155221101206 35645149
    [Google Scholar]
  153. Beheshti Namdar A. Kabiri M. Mosanan Mozaffari H. Aminifar E. Mehrad-Majd H. Circulating clusterin levels and cancer risk: A systematic review and meta-analysis. Cancer Contr. 2022 29 10.1177/10732748211038437 35465749
    [Google Scholar]
  154. Hellman N.E. Gitlin J.D. Ceruloplasmin metabolism and function. Annu. Rev. Nutr. 2002 22 1 439 458 10.1146/annurev.nutr.22.012502.114457 12055353
    [Google Scholar]
  155. Banha J. Marques L. Oliveira R. Martins M.F. Paixão E. Pereira D. Malhó R. Penque D. Costa L. Ceruloplasmin expression by human peripheral blood lymphocytes: A new link between immunity and iron metabolism. Free Radic. Biol. Med. 2008 44 3 483 492 10.1016/j.freeradbiomed.2007.10.032 17991445
    [Google Scholar]
  156. Kim O.Y. Shin M.J. Moon J. Chung J.H. Plasma ceruloplasmin as a biomarker for obesity: A proteomic approach. Clin. Biochem. 2011 44 5-6 351 356 10.1016/j.clinbiochem.2011.01.014 21291874
    [Google Scholar]
  157. Marques L. Auriac A. Willemetz A. Banha J. Silva B. Canonne-Hergaux F. Costa L. Immune cells and hepatocytes express glycosylphosphatidylinositol-anchored ceruloplasmin at their cell surface. Blood Cells Mol. Dis. 2012 48 2 110 120 10.1016/j.bcmd.2011.11.005 22178061
    [Google Scholar]
  158. Bielli P. Calabrese L. Structure to function relationships in ceruloplasmin: A ‘moonlighting’ protein. Cell. Mol. Life Sci. 2002 59 9 1413 1427 10.1007/s00018‑002‑8519‑2 12440766
    [Google Scholar]
  159. Liu Z. Wang M. Zhang C. Zhou S. Ji G. Molecular functions of ceruloplasmin in metabolic disease pathology. Diabetes Metab. Syndr. Obes. 2022 15 695 711 10.2147/DMSO.S346648 35264864
    [Google Scholar]
  160. Golizeh M. Lee K. Ilchenko S. Ösme A. Bena J. Sadygov R.G. Kashyap S.R. Kasumov T. Increased serotransferrin and ceruloplasmin turnover in diet-controlled patients with type 2 diabetes. Free Radic. Biol. Med. 2017 113 461 469 10.1016/j.freeradbiomed.2017.10.373 29079528
    [Google Scholar]
  161. Kim C.H. Park J.Y. Kim J.Y. Choi C.S. Kim Y.I. Chung Y.E. Lee M.S. Hong S.K. Lee K.U. Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: A population-based study. Metabolism 2002 51 7 838 842 10.1053/meta.2002.33348 12077727
    [Google Scholar]
  162. Xia Z. Hu M. Zheng L. Zheng E. Deng M. Wu J. Sheng X. Assessing whether serum ceruloplasmin promotes non-alcoholic steatohepatitis via regulating iron metabolism. J. Med. Biochem. 2023 42 1 113 121 10.5937/jomb0‑37597 36819130
    [Google Scholar]
  163. Xie L. Yuan Y. Xu S. Lu S. Gu J. Wang Y. Wang Y. Zhang X. Chen S. Li J. Lu J. Sun H. Hu R. Piao H. Wang W. Wang C. Wang J. Li N. White M.F. Han L. Jia W. Miao J. Liu J. Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex. Cell Rep. 2022 41 3 111498 10.1016/j.celrep.2022.111498 36261001
    [Google Scholar]
  164. Jiang Q. Wang N. Lu S. Xiong J. Yuan Y. Liu J. Chen S. Targeting hepatic ceruloplasmin mitigates nonalcoholic steatohepatitis by modulating bile acid metabolism. J. Mol. Cell Biol. 2024 15 9 mjad060 10.1093/jmcb/mjad060 37771074
    [Google Scholar]
  165. Nunes V.S. Andrade A.R. Guedes A.L.V. Diniz M.A. Oliveira C.P. Distinct phenotype of non-alcoholic fatty liver disease in patients with low levels of free copper and of ceruloplasmin. Arq. Gastroenterol. 2020 57 249 253 10.1590/s0004‑2803.202000000‑47 32935743
    [Google Scholar]
  166. Lopez M.J. Royer A. Shah N. Biochemistry, Ceruloplasmin. StatPearls Publishing Treasure Island, FL 2024
    [Google Scholar]
  167. Mackness M. Mackness B. Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene 2015 567 1 12 21 10.1016/j.gene.2015.04.088 25965560
    [Google Scholar]
  168. Grdic Rajkovic M. Rumora L. Barisic K. The paraoxonase 1, 2 and 3 in humans. Biochem. Med. (Zagreb) 2011 21 2 122 130 10.11613/BM.2011.020 22135851
    [Google Scholar]
  169. Deakin S. Leviev I. Gomaraschi M. Calabresi L. Franceschini G. James R.W. Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J. Biol. Chem. 2002 277 6 4301 4308 10.1074/jbc.M107440200 11726658
    [Google Scholar]
  170. Rodrigo L. Hernández A.F. López-Caballero J.J. Gil F. Pla A. Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. implications for its physiological role. Chem. Biol. Interact. 2001 137 2 123 137 10.1016/S0009‑2797(01)00225‑3 11551529
    [Google Scholar]
  171. Kotani K. Watanabe J. Miura K. Gugliucci A. Paraoxonase 1 and non-alcoholic fatty liver disease: A meta-analysis. Molecules 2021 26 8 2323 10.3390/molecules26082323 33923656
    [Google Scholar]
  172. Atamer A. Bilici A. Yenice N. Selek S. Ilhan N. Atamer Y. The importance of paraoxonase 1 activity, nitric oxide and lipid peroxidation in hepatosteatosis. J. Int. Med. Res. 2008 36 4 771 776 10.1177/147323000803600419 18652773
    [Google Scholar]
  173. Desai S. Baker S.S. Liu W. Moya D.A. Browne R.W. Mastrandrea L. Baker R.D. Zhu L. Paraoxonase 1 and oxidative stress in paediatric non‐alcoholic steatohepatitis. Liver Int. 2014 34 1 110 117 10.1111/liv.12308 24028323
    [Google Scholar]
  174. Fedelesova M. Kupcova V. Luha J. Turecky L. Paraoxonase activity in sera of patients with non-alcoholic fatty liver disease. Bratisl. Lek Listy 2017 118 12 719 720 29322801
    [Google Scholar]
  175. García-Heredia A. Kensicki E. Mohney R.P. Rull A. Triguero I. Marsillach J. Tormos C. Mackness B. Mackness M. Shih D.M. Pedro-Botet J. Joven J. Sáez G. Camps J. Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet: A metabolomic approach. J. Proteome Res. 2013 12 4 1946 1955 10.1021/pr400050u 23448543
    [Google Scholar]
  176. Rozenberg O. Shih D.M. Aviram M. Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: Possible role for its phospholipase-A2-like activity and lysophosphatidylcholine formation. Arterioscler. Thromb. Vasc. Biol. 2003 23 3 461 467 10.1161/01.ATV.0000060462.35946.B3 12615663
    [Google Scholar]
  177. Cheung K.J. Tilleman K. Deforce D. Colle I. Van Vlierberghe H. The HCV serum proteome: A search for fibrosis protein markers. J. Viral Hepat. 2009 16 6 418 429 10.1111/j.1365‑2893.2009.01083.x 19226329
    [Google Scholar]
  178. Przybyło M. Martuszewska D. Pocheć E. Hoja-Łukowicz D. Lityńska A. Identification of proteins bearing β1–6 branched N-glycans in human melanoma cell lines from different progression stages by tandem mass spectrometry analysis. Biochim. Biophys. Acta, Gen. Subj. 2007 1770 9 1427 1435 10.1016/j.bbagen.2007.05.006 17600626
    [Google Scholar]
  179. Xu Q. Feng M. Ren Y. Liu X. Gao H. Li Z. Su X. Wang Q. Wang Y. From NAFLD to HCC: Advances in noninvasive diagnosis. Biomed. Pharmacother. 2023 165 115028 10.1016/j.biopha.2023.115028 37331252
    [Google Scholar]
  180. Kamada Y. Ono M. Hyogo H. Fujii H. Sumida Y. Mori K. Tanaka S. Yamada M. Akita M. Mizutani K. Fujii H. Yamamoto A. Takamatsu S. Yoshida Y. Itoh Y. Kawada N. Chayama K. Saibara T. Takehara T. Miyoshi E. A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers. Hepatology 2015 62 5 1433 1443 10.1002/hep.28002 26199205
    [Google Scholar]
  181. Kamada Y. Ono M. Hyogo H. Fujii H. Sumida Y. Yamada M. Mori K. Tanaka S. Maekawa T. Ebisutani Y. Yamamoto A. Takamatsu S. Yoneda M. Kawada N. Chayama K. Saibara T. Takehara T. Miyoshi E. Use of Mac‐2 binding protein as a biomarker for nonalcoholic fatty liver disease diagnosis. Hepatol. Commun. 2017 1 8 780 791 10.1002/hep4.1080 29404494
    [Google Scholar]
  182. Kamada Y. Morishita K. Koseki M. Nishida M. Asuka T. Naito Y. Yamada M. Takamatsu S. Sakata Y. Takehara T. Miyoshi E. Serum Mac-2 binding protein levels associate with metabolic parameters and predict liver fibrosis progression in subjects with fatty liver disease: A 7-year longitudinal study. Nutrients 2020 12 6 1770 10.3390/nu12061770 32545650
    [Google Scholar]
  183. Abe M. Miyake T. Kuno A. Imai Y. Sawai Y. Hino K. Hara Y. Hige S. Sakamoto M. Yamada G. Kage M. Korenaga M. Hiasa Y. Mizokami M. Narimatsu H. Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease. J. Gastroenterol. 2015 50 7 776 784 10.1007/s00535‑014‑1007‑2 25326152
    [Google Scholar]
  184. Ito K. Murotani K. Nakade Y. Inoue T. Nakao H. Sumida Y. Kamada Y. Yoneda M. Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein levels and liver fibrosis: A meta‐analysis. J. Gastroenterol. Hepatol. 2017 32 12 1922 1930 10.1111/jgh.13802 28406534
    [Google Scholar]
  185. Jang S.Y. Tak W.Y. Park S.Y. Kweon Y.O. Lee Y.R. Kim G. Hur K. Han M.H. Lee W.K. Diagnostic efficacy of serum Mac-2 binding protein glycosylation isomer and other markers for liver fibrosis in non-alcoholic fatty liver diseases. Ann. Lab. Med. 2021 41 3 302 309 10.3343/alm.2021.41.3.302 33303715
    [Google Scholar]
  186. Fernandes C.L. Ligabue-Braun R. Verli H. Structural glycobiology of human α 1 -acid glycoprotein and its implications for pharmacokinetics and inflammation. Glycobiology 2015 25 10 1125 1133 10.1093/glycob/cwv041 26088564
    [Google Scholar]
  187. Ceciliani F. Lecchi C. The immune functions of α 1 acid glycoprotein. Curr. Protein Pept. Sci. 2019 20 6 505 524 10.2174/1389203720666190405101138 30950347
    [Google Scholar]
  188. Fournier T. Medjoubi-N N. Porquet D. Alpha-1-acid glycoprotein. Biochim. Biophys. Acta Protein Struct. Mol. Enzymol. 2000 1482 1-2 157 171 10.1016/S0167‑4838(00)00153‑9 11058758
    [Google Scholar]
  189. Ceciliani F. Pocacqua V. The acute phase protein alpha1-acid glycoprotein: A model for altered glycosylation during diseases. Curr. Protein Pept. Sci. 2007 8 1 91 108 10.2174/138920307779941497 17305563
    [Google Scholar]
  190. K, T.; K, K.; N, K.; S, I. Multifucosylated Alpha-1-Acid Glycoprotein as a Novel Marker for Hepatocellular Carcinoma. J. Proteome Res. 2016 15
    [Google Scholar]
  191. Åström E. Stål P. Zenlander R. Edenvik P. Alexandersson C. Haglund M. Rydén I. Påhlsson P. Reverse lectin ELISA for detecting fucosylated forms of α1-acid glycoprotein associated with hepatocellular carcinoma. PLoS One 2017 12 3 e0173897 10.1371/journal.pone.0173897 28296934
    [Google Scholar]
  192. Gani R.A. Suryamin M. Hasan I. Lesmana C.R.A. Sanityoso A. Performance of alpha fetoprotein in combination with Alpha-1-acid Glycoprotein for diagnosis of hepatocellular carcinoma among liver cirrhosis patients. Acta Med. Indones. 2015 47 3 216 222 26586387
    [Google Scholar]
  193. Zhang D. Huang J. Luo D. Feng X. Liu Y. Liu Y. Glycosylation change of alpha-1-acid glycoprotein as a serum biomarker for hepatocellular carcinoma and cirrhosis. Biomarkers Med. 2017 11 5 423 430 10.2217/bmm‑2016‑0284 28621608
    [Google Scholar]
  194. Huhn C. Selman M.H.J. Ruhaak L.R. Deelder A.M. Wuhrer M. IgG glycosylation analysis. Proteomics 2009 9 4 882 913 10.1002/pmic.200800715 19212958
    [Google Scholar]
  195. Zhao Z.Y. Liu D. Cao W.J. Sun M. Song M.S. Wang W. Wang Y.X. Association between IgG N-glycans and nonalcoholic fatty liver disease in Han Chinese. Biomed. Environ. Sci. 2018 31 6 454 458 30025558
    [Google Scholar]
  196. Yuan W. Sanda M. Wu J. Koomen J. Goldman R. Quantitative analysis of immunoglobulin subclasses and subclass specific glycosylation by LC–MS–MRM in liver disease. J. Proteomics 2015 116 24 33 10.1016/j.jprot.2014.12.020 25582524
    [Google Scholar]
  197. Olubuyide I.O. Salimonu L.S. Adeniran S.O. Soluble immune complexes and immunoglobulin (IgG, IgA and IgM) levels in Nigerians with primary liver cell carcinoma. Afr. J. Med. Med. Sci. 1993 22 4 57 62 7839931
    [Google Scholar]
  198. Yi C.H. Weng H.L. Zhou F.G. Fang M. Ji J. Cheng C. Wang H. Liebe R. Dooley S. Gao C.F. Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma. OncoImmunology 2015 4 12 e1011503 10.1080/2162402X.2015.1011503 26587313
    [Google Scholar]
  199. Sun Z. Fu B. Wang G. Zhang L. Xu R. Zhang Y. Lu H. High-throughput site-specific N -glycoproteomics reveals glyco-signatures for liver disease diagnosis. Natl. Sci. Rev. 2023 10 1 nwac059 10.1093/nsr/nwac059 36879659
    [Google Scholar]
  200. Liu X. Fu B. Chen J. Sun Z. Zheng D. Li Z. Gu B. Zhang Y. Lu H. High-throughput intact Glycopeptide quantification strategy with targeted-MS (HTiGQs-target) reveals site-specific IgG N-glycopeptides as biomarkers for hepatic disorder diagnosis and staging. Carbohydr. Polym. 2024 325 121499 10.1016/j.carbpol.2023.121499 38008487
    [Google Scholar]
  201. Delanghe J.R. Langlois M.R. Hemopexin: A review of biological aspects and the role in laboratory medicine. Clin. Chim. Acta 2001 312 1-2 13 23 10.1016/S0009‑8981(01)00586‑1 11580905
    [Google Scholar]
  202. Tolosano E. Altruda F. Hemopexin: Structure, function, and regulation. DNA Cell Biol. 2002 21 4 297 306 10.1089/104454902753759717 12042069
    [Google Scholar]
  203. Fiorito V. Chiabrando D. Petrillo S. Bertino F. Tolosano E. The multifaceted role of heme in cancer. Front. Oncol. 2020 9 1540 10.3389/fonc.2019.01540 32010627
    [Google Scholar]
  204. Ma J. Sanda M. Wei R. Zhang L. Goldman R. Quantitative analysis of core fucosylation of serum proteins in liver diseases by LC-MS-MRM. J. Proteomics 2018 189 67 74 10.1016/j.jprot.2018.02.003 29427759
    [Google Scholar]
  205. Benicky J. Sanda M. Pompach P. Wu J. Goldman R. Quantification of fucosylated hemopexin and complement factor H in plasma of patients with liver disease. Anal. Chem. 2014 86 21 10716 10723 10.1021/ac502727s 25302577
    [Google Scholar]
  206. Zhao Y. Sato Y. Isaji T. Fukuda T. Matsumoto A. Miyoshi E. Gu J. Taniguchi N. Branched N‐glycans regulate the biological functions of integrins and cadherins. FEBS J. 2008 275 9 1939 1948 10.1111/j.1742‑4658.2008.06346.x 18384383
    [Google Scholar]
  207. Debruyne E.N. Vanderschaeghe D. Van Vlierberghe H. Vanhecke A. Callewaert N. Delanghe J.R. Diagnostic value of the hemopexin N-glycan profile in hepatocellular carcinoma patients. Clin. Chem. 2010 56 5 823 831 10.1373/clinchem.2009.139295 20348404
    [Google Scholar]
/content/journals/cp/10.2174/0115701646341608241025030547
Loading
Decoding Glycobiomarkers in Non-Alcoholic Steatohepatitis (NASH) and Related Hepatocellular Carcinoma (HCC)
Bentham Science Publishers ; https://doi.org/10.2174/0115701646341608241025030547
/content/journals/cp/10.2174/0115701646341608241025030547
/content/journals/cp/10.2174/0115701646341608241025030547
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: hepatocarcinogenesis ; glycoproteins ; non-alcoholic steatohepatitis (NASH) ; glycosylation ; biomarkers ; Hepatocellular carcinoma (HCC)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test