Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Cancer Drug Targets
  4. Fast Track Articles
  5. Fast Track Article
image of Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis

Abstract

Background

Lung adenocarcinoma (LUAD) is a highly lethal malignancy. Liquid-Liquid Phase Separation (LLPS) plays a crucial role in targeted therapies for lung cancer and in the progression of lung squamous cell carcinoma. However, the role of LLPS in the progression and prognosis of LUAD remains insufficiently explored.

Methods

This study employed a multi-step approach to identify LLPS prognosis-related genes in LUAD. First, differential analysis, univariate Cox regression analysis, Random Survival Forest (RSF) method, and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis were utilized to identify five LLPS prognosis-related genes. Subsequently, LASSO Cox regression was performed to establish a prognostic score termed the LLPS-related prognosis score (LPRS). Comprehensive analyses were then conducted based on the LPRS, including survival analysis, clinical feature analysis, functional enrichment analysis, and tumor microenvironment assessment. The LPRS was integrated with additional clinicopathological factors to develop a prognostic nomogram for LUAD patients. Immunohistochemical validation was performed on clinical tissue samples to further validate the findings. Finally, the relationship between KRT6A, one of the identified genes, and epidermal growth factor receptor (EGFR) mutations was investigated.

Results

The LPRS was established using five LLPS-related genes: IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. Higher LPRS was closely associated with poor survival outcomes, gender, progression-free survival (PFS), and advanced TNM stage. Furthermore, LPRS emerged as an independent prognostic factor for LUAD. A nomogram integrating LPRS, TNM stage, and age demonstrated remarkable predictive accuracy for prognosis among patients with LUAD. LLPS likely influences LUAD prognosis through the activity of IGF2BP1, KRT6A, LDHA, PKP2, and PLK1. KRT6A exhibits significant upregulation in LUAD, particularly in patients with EGFR mutations.

Conclusion

This study introduces a novel LPRS model that demonstrates high accuracy in predicting the clinical prognosis of LUAD. Moreover, the findings suggest that KRT6A may play a critical role in the LLPS-mediated malignant progression of LUAD.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096345676241001081051
2024-11-06
2025-01-18

  • From This Site

    /content/journals/ccdt/10.2174/0115680096345676241001081051
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Thai A.A. Solomon B.J. Sequist L.V. Gainor J.F. Heist R.S. Lung cancer. Lancet 2021 398 10299 535 554 10.1016/S0140‑6736(21)00312‑3 34273294
    [Google Scholar]
  2. Forde P.M. Spicer J. Lu S. Provencio M. Mitsudomi T. Awad M.M. Felip E. Broderick S.R. Brahmer J.R. Swanson S.J. Kerr K. Wang C. Ciuleanu T.E. Saylors G.B. Tanaka F. Ito H. Chen K.N. Liberman M. Vokes E.E. Taube J.M. Dorange C. Cai J. Fiore J. Jarkowski A. Balli D. Sausen M. Pandya D. Calvet C.Y. Girard N. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N. Engl. J. Med. 2022 386 21 1973 1985 10.1056/NEJMoa2202170 35403841
    [Google Scholar]
  3. Li Y. Yan B. He S. Advances and challenges in the treatment of lung cancer. Biomed. Pharmacother. 2023 169 115891 10.1016/j.biopha.2023.115891 37979378
    [Google Scholar]
  4. Abdelaziz H.M. Gaber M. Abd-Elwakil M.M. Mabrouk M.T. Elgohary M.M. Kamel N.M. Kabary D.M. Freag M.S. Samaha M.W. Mortada S.M. Elkhodairy K.A. Fang J.Y. Elzoghby A.O. Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates. J. Control. Release 2018 269 374 392 10.1016/j.jconrel.2017.11.036 29180168
    [Google Scholar]
  5. Schabath M.B. Cote M.L. Cancer progress and priorities: Lung cancer. Cancer Epidemiol. Biomarkers Prev. 2019 28 10 1563 1579 10.1158/1055‑9965.EPI‑19‑0221 31575553
    [Google Scholar]
  6. Shi F. Li L. Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of the Rapamycin Pathway-Related Protein Expression in Lung Squamous Cell Carcinoma and Its Correlation with Lymph Node Metastasis. J. Oncol. 2022 2022 1 7 10.1155/2022/4537256 36052284
    [Google Scholar]
  7. Wu J. Lin Z. Non-small cell lung cancer targeted therapy: Drugs and mechanisms of drug resistance. Int. J. Mol. Sci. 2022 23 23 15056 10.3390/ijms232315056 36499382
    [Google Scholar]
  8. Imyanitov E.N. Iyevleva A.G. Levchenko E.V. Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives. Crit. Rev. Oncol. Hematol. 2021 157 103194 10.1016/j.critrevonc.2020.103194 33316418
    [Google Scholar]
  9. Tan A.C. Tan D.S.W. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J. Clin. Oncol. 2022 40 6 611 625 10.1200/JCO.21.01626 34985916
    [Google Scholar]
  10. Herrera-Juárez M. Serrano-Gómez C. Bote-de-Cabo H. Paz-Ares L. Targeted therapy for lung cancer: Beyond EGFR and ALK. Cancer 2023 129 12 1803 1820 10.1002/cncr.34757 37073562
    [Google Scholar]
  11. Hirsch F.R. Scagliotti G.V. Mulshine J.L. Kwon R. Curran W.J. Jr Wu Y.L. Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet 2017 389 10066 299 311 10.1016/S0140‑6736(16)30958‑8 27574741
    [Google Scholar]
  12. Fu K. Xie F. Wang F. Fu L. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J. Hematol. Oncol. 2022 15 1 173 10.1186/s13045‑022‑01391‑4 36482474
    [Google Scholar]
  13. Chen P. Liu Y. Wen Y. Zhou C. Non‐small cell lung cancer in China. Cancer Commun. (Lond.) 2022 42 10 937 970 10.1002/cac2.12359 36075878
    [Google Scholar]
  14. Zombori T. Sejben A. Tiszlavicz L. Cserni G. Pálföldi R. Csada E. Furák J. Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas. Pathol. Oncol. Res. 2020 26 4 2451 2458 10.1007/s12253‑020‑00855‑7 32564261
    [Google Scholar]
  15. He J. Huang Z. Han L. Gong Y. Xie C. Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer. Int. J. Oncol. 2021 59 5 90 10.3892/ijo.2021.5270 34558640
    [Google Scholar]
  16. Blaquier J.B. Ortiz-Cuaran S. Ricciuti B. Mezquita L. Cardona A.F. Recondo G. Tackling osimertinib resistance in EGFR-mutant non–small cell lung cancer. Clin. Cancer Res. 2023 29 18 3579 3591 10.1158/1078‑0432.CCR‑22‑1912 37093192
    [Google Scholar]
  17. Passaro A. Jänne P.A. Mok T. Peters S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat. Cancer 2021 2 4 377 391 10.1038/s43018‑021‑00195‑8 35122001
    [Google Scholar]
  18. Bertoli E. De Carlo E. Del Conte A. Stanzione B. Revelant A. Fassetta K. Spina M. Bearz A. Acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer: How do we overcome it? Int. J. Mol. Sci. 2022 23 13 6936 10.3390/ijms23136936 35805940
    [Google Scholar]
  19. Cooper A.J. Sequist L.V. Lin J.J. Third-generation EGFR and ALK inhibitors: Mechanisms of resistance and management. Nat. Rev. Clin. Oncol. 2022 19 8 499 514 10.1038/s41571‑022‑00639‑9 35534623
    [Google Scholar]
  20. Mehta S. Zhang J. Liquid–liquid phase separation drives cellular function and dysfunction in cancer. Nat. Rev. Cancer 2022 22 4 239 252 10.1038/s41568‑022‑00444‑7 35149762
    [Google Scholar]
  21. Szała-Mendyk B. Phan T.M. Mohanty P. Mittal J. Challenges in studying the liquid-to-solid phase transitions of proteins using computer simulations. Curr. Opin. Chem. Biol. 2023 75 102333 10.1016/j.cbpa.2023.102333 37267850
    [Google Scholar]
  22. Bracha D. Walls M.T. Brangwynne C.P. Probing and engineering liquid-phase organelles. Nat. Biotechnol. 2019 37 12 1435 1445 10.1038/s41587‑019‑0341‑6 31792412
    [Google Scholar]
  23. Alberti S. Hyman A.A. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. Nat. Rev. Mol. Cell Biol. 2021 22 3 196 213 10.1038/s41580‑020‑00326‑6 33510441
    [Google Scholar]
  24. Wiedner H.J. Giudice J. It’s not just a phase: Function and characteristics of RNA-binding proteins in phase separation. Nat. Struct. Mol. Biol. 2021 28 6 465 473 10.1038/s41594‑021‑00601‑w 34099940
    [Google Scholar]
  25. Wagh K. Garcia D.A. Upadhyaya A. Phase separation in transcription factor dynamics and chromatin organization. Curr. Opin. Struct. Biol. 2021 71 148 155 10.1016/j.sbi.2021.06.009 34303933
    [Google Scholar]
  26. Cheng Y. Xie W. Pickering B.F. Chu K.L. Savino A.M. Yang X. Luo H. Nguyen D.T.T. Mo S. Barin E. Velleca A. Rohwetter T.M. Patel D.J. Jaffrey S.R. Kharas M.G. N6-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation. Cancer Cell 2021 39 7 958 972.e8 10.1016/j.ccell.2021.04.017 34048709
    [Google Scholar]
  27. Pakravan D. Orlando G. Bercier V. Van Den Bosch L. Role and therapeutic potential of liquid–liquid phase separation in amyotrophic lateral sclerosis. J. Mol. Cell Biol. 2021 13 1 15 28 10.1093/jmcb/mjaa049 32976566
    [Google Scholar]
  28. Kanekura K. Kuroda M. How can we interpret the relationship between liquid-liquid phase separation and amyotrophic lateral sclerosis? Lab. Invest. 2022 102 9 912 918 10.1038/s41374‑022‑00791‑x 35459796
    [Google Scholar]
  29. Ainani H. Bouchmaa N. Ben Mrid R. El Fatimy R. Liquid-liquid phase separation of protein tau: An emerging process in Alzheimer’s disease pathogenesis. Neurobiol. Dis. 2023 178 106011 10.1016/j.nbd.2023.106011 36702317
    [Google Scholar]
  30. Boyko S. Surewicz W.K. Tau liquid–liquid phase separation in neurodegenerative diseases. Trends Cell Biol. 2022 32 7 611 623 10.1016/j.tcb.2022.01.011 35181198
    [Google Scholar]
  31. Fu Q. Zhang B. Chen X. Chu L. Liquid–liquid phase separation in Alzheimer’s disease. J. Mol. Med. (Berl.) 2024 102 2 167 181 10.1007/s00109‑023‑02407‑3 38167731
    [Google Scholar]
  32. Relli V. Trerotola M. Guerra E. Alberti S. Abandoning the notion of non-small cell lung cancer. Trends Mol. Med. 2019 25 7 585 594 10.1016/j.molmed.2019.04.012 31155338
    [Google Scholar]
  33. Wang B. Zhang L. Dai T. Qin Z. Lu H. Zhang L. Zhou F. Liquid–liquid phase separation in human health and diseases. Signal Transduct. Target. Ther. 2021 6 1 290 10.1038/s41392‑021‑00678‑1 34334791
    [Google Scholar]
  34. Zou Y. Zheng H. Ning Y. Yang Y. Wen Q. Fan S. New insights into the important roles of phase seperation in the targeted therapy of lung cancer. Cell Biosci. 2023 13 1 150 10.1186/s13578‑023‑01101‑8 37580790
    [Google Scholar]
  35. Klein I.A. Boija A. Afeyan L.K. Hawken S.W. Fan M. Dall’Agnese A. Oksuz O. Henninger J.E. Shrinivas K. Sabari B.R. Sagi I. Clark V.E. Platt J.M. Kar M. McCall P.M. Zamudio A.V. Manteiga J.C. Coffey E.L. Li C.H. Hannett N.M. Guo Y.E. Decker T.M. Lee T.I. Zhang T. Weng J.K. Taatjes D.J. Chakraborty A. Sharp P.A. Chang Y.T. Hyman A.A. Gray N.S. Young R.A. Partitioning of cancer therapeutics in nuclear condensates. Science 2020 368 6497 1386 1392 10.1126/science.aaz4427 32554597
    [Google Scholar]
  36. Tong X. Tang R. Xu J. Wang W. Zhao Y. Yu X. Shi S. Liquid–liquid phase separation in tumor biology. Signal Transduct. Target. Ther. 2022 7 1 221 10.1038/s41392‑022‑01076‑x 35803926
    [Google Scholar]
  37. Peng P-H. Hsu K-W. Wu K-J. Liquid-liquid phase separation (LLPS) in cellular physiology and tumor biology. Am. J. Cancer Res. 2021 11 8 3766 3776 34522448
    [Google Scholar]
  38. Liu Z. Qin Z. Liu Y. Xia X. He L. Chen N. Hu X. Peng X. Liquid‒liquid phase separation: roles and implications in future cancer treatment. Int. J. Biol. Sci. 2023 19 13 4139 4156 10.7150/ijbs.81521 37705755
    [Google Scholar]
  39. Xie Q. Cheng J. Mei W. Yang D. Zhang P. Zeng C. Phase separation in cancer at a glance. J. Transl. Med. 2023 21 1 237 10.1186/s12967‑023‑04082‑x 37005672
    [Google Scholar]
  40. Xiao C. Wu G. Chen P. Gao L. Chen G. Zhang H. Phase separation in epigenetics and cancer stem cells. Front. Oncol. 2022 12 922604 10.3389/fonc.2022.922604 36081552
    [Google Scholar]
  41. Peng Q. Tan S. Xia L. Wu N. Oyang L. Tang Y. Su M. Luo X. Wang Y. Sheng X. Zhou Y. Liao Q. Phase separation in Cancer: From the Impacts and Mechanisms to Treatment potentials. Int. J. Biol. Sci. 2022 18 13 5103 5122 10.7150/ijbs.75410 35982902
    [Google Scholar]
  42. Jiang X. Zhang Y. Wang H. Wang Z. Hu S. Cao C. Xiao H. In-depth metaproteomics analysis of oral microbiome for lung cancer. Research 2022 2022 2022/9781578 10.34133/2022/9781578 36320634
    [Google Scholar]
  43. Liu C. Qin Q. Cong H. Research progress on the relationship between mitochondrial deoxyguanosine kinase and apoptosis and autophagy in lung adenocarcinoma cells. Cancer Insight 2022 1 1 8 10.58567/ci01010004
    [Google Scholar]
  44. Huang H. Weng H. Sun W. Qin X. Shi H. Wu H. Zhao B.S. Mesquita A. Liu C. Yuan C.L. Hu Y.C. Hüttelmaier S. Skibbe J.R. Su R. Deng X. Dong L. Sun M. Li C. Nachtergaele S. Wang Y. Hu C. Ferchen K. Greis K.D. Jiang X. Wei M. Qu L. Guan J.L. He C. Yang J. Chen J. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat. Cell Biol. 2018 20 3 285 295 10.1038/s41556‑018‑0045‑z 29476152
    [Google Scholar]
  45. Korn S.M. Ulshöfer C.J. Schneider T. Schlundt A. Structures and target RNA preferences of the RNA-binding protein family of IGF2BPs: An overview. Structure 2021 29 8 787 803 10.1016/j.str.2021.05.001 34022128
    [Google Scholar]
  46. Peng W. Ye L. Xue Q. Wei X. Wang Z. Xiang X. Zhang S. Zhang P. Wang H. Zhou Q. Silencing of circCRIM1 Drives IGF2BP1-Mediated NSCLC Immune Evasion. Cells 2023 12 2 273 10.3390/cells12020273 36672208
    [Google Scholar]
  47. Zhu Q. Zhang C. Qu T. Lu X. He X. Li W. Yin D. Han L. Guo R. Zhang E. MNX1-AS1 promotes phase separation of IGF2BP1 to Drive c-Myc–mediated cell-cycle progression and proliferation in lung cancer. Cancer Res. 2022 82 23 4340 4358 10.1158/0008‑5472.CAN‑22‑1289 36214649
    [Google Scholar]
  48. Zeng W. Lu C. Shi Y. Wu C. Chen X. Li C. Yao J. Initiation of stress granule assembly by rapid clustering of IGF2BP proteins upon osmotic shock. Biochim. Biophys. Acta Mol. Cell Res. 2020 1867 10 118795 10.1016/j.bbamcr.2020.118795 32668274
    [Google Scholar]
  49. Yang B. Zhang W. Zhang M. Wang X. Peng S. Zhang R. KRT6A promotes EMT and cancer stem cell transformation in lung adenocarcinoma. Technol. Cancer Res. Treat. 2020 19 10.1177/1533033820921248 32329414
    [Google Scholar]
  50. Xiao J. Lu X. Chen X. Zou Y. Liu A. Li W. He B. He S. Chen Q. Eight potential biomarkers for distinguishing between lung adenocarcinoma and squamous cell carcinoma. Oncotarget 2017 8 42 71759 71771 10.18632/oncotarget.17606 29069744
    [Google Scholar]
  51. Zhou J. Jiang G. Xu E. Zhou J. Liu L. Yang Q. Identification of SRXN1 and KRT6A as key genes in smoking-related non-small-cell lung cancer through bioinformatics and functional analyses. Front. Oncol. 2022 11 810301 10.3389/fonc.2021.810301 35071014
    [Google Scholar]
  52. Che D. Wang M. Sun J. Li B. Xu T. Lu Y. Pan H. Lu Z. Gu X. KRT6A promotes lung cancer cell growth and invasion through MYC-regulated pentose phosphate pathway. Front. Cell Dev. Biol. 2021 9 694071 10.3389/fcell.2021.694071 34235156
    [Google Scholar]
  53. Bai Y. Qi W. Liu L. Zhang J. Pang L. Gan T. Wang P. Wang C. Chen H. Identification of seven-gene hypoxia signature for predicting overall survival of hepatocellular carcinoma. Front. Genet. 2021 12 637418 10.3389/fgene.2021.637418 33912215
    [Google Scholar]
  54. Yu X. Zhang X. Zhang Y. Identification of a 5-gene metabolic signature for predicting prognosis based on an integrated analysis of tumor microenvironment in lung adenocarcinoma. J. Oncol. 2020 2020 1 12 10.1155/2020/5310793 32684932
    [Google Scholar]
  55. Comandatore A. Franczak M. Smolenski R.T. Morelli L. Peters G.J. Giovannetti E. Lactate Dehydrogenase and its clinical significance in pancreatic and thoracic cancers. Semin. Cancer Biol. 2022 86 Pt 2 93 100 10.1016/j.semcancer.2022.09.001 36096316
    [Google Scholar]
  56. Hao X.L. Tian Z. Han F. Chen J.P. Gao L.Y. Liu J.Y. Plakophilin-2 accelerates cell proliferation and migration through activating EGFR signaling in lung adenocarcinoma. Pathol. Res. Pract. 2019 215 7 152438 10.1016/j.prp.2019.152438 31126818
    [Google Scholar]
  57. Cong D. Zhao Y. Zhang W. Li J. Bai Y. Applying machine learning algorithms to develop a survival prediction model for lung adenocarcinoma based on genes related to fatty acid metabolism. Front. Pharmacol. 2023 14 1260742 10.3389/fphar.2023.1260742 37920207
    [Google Scholar]
  58. Wu Y. Liu L. Shen X. Liu W. Ma R. Plakophilin-2 promotes lung adenocarcinoma development via enhancing focal adhesion and epithelial–mesenchymal transition. Cancer Manag. Res. 2021 13 559 570 10.2147/CMAR.S281663 33519235
    [Google Scholar]
  59. Arimoto K. Burkart C. Yan M. Ran D. Weng S. Zhang D.E. Plakophilin-2 promotes tumor development by enhancing ligand-dependent and -independent epidermal growth factor receptor dimerization and activation. Mol. Cell. Biol. 2014 34 20 3843 3854 10.1128/MCB.00758‑14 25113560
    [Google Scholar]
  60. Liu Z. Sun Q. Wang X. PLK1, a potential target for cancer therapy. Transl. Oncol. 2017 10 1 22 32 10.1016/j.tranon.2016.10.003 27888710
    [Google Scholar]
  61. Iliaki S. Beyaert R. Afonina I.S. Polo-like kinase 1 (PLK1) signaling in cancer and beyond. Biochem. Pharmacol. 2021 193 114747 10.1016/j.bcp.2021.114747 34454931
    [Google Scholar]
  62. Su S. Chhabra G. Singh C.K. Ndiaye M.A. Ahmad N. PLK1 inhibition-based combination therapies for cancer management. Transl. Oncol. 2022 16 101332 10.1016/j.tranon.2021.101332 34973570
    [Google Scholar]
  63. Wang Z.X. Xue D. Liu Z.L. Lu B.B. Bian H.B. Pan X. Yin Y.M. Overexpression of polo-like kinase 1 and its clinical significance in human non-small cell lung cancer. Int. J. Biochem. Cell Biol. 2012 44 1 200 210 10.1016/j.biocel.2011.10.017 22064247
    [Google Scholar]
  64. Reda M. Ngamcherdtrakul W. Gu S. Bejan D.S. Siriwon N. Gray J.W. Yantasee W. PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer. Cancer Lett. 2019 467 9 18 10.1016/j.canlet.2019.09.014 31563561
    [Google Scholar]
  65. Inoue M. Yoshimura M. Kobayashi M. Morinibu A. Itasaka S. Hiraoka M. Harada H. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase. Sci. Rep. 2015 5 1 15666 10.1038/srep15666 26503893
    [Google Scholar]
  66. Boija A. Klein I.A. Young R.A. Biomolecular Condensates and Cancer. Cancer Cell 2021 39 2 174 192 10.1016/j.ccell.2020.12.003 33417833
    [Google Scholar]
  67. Zhan Y. Wang H. Ning Y. Zheng H. Liu S. Yang Y. Zhou M. Fan S. Understanding the roles of stress granule during chemotherapy for patients with malignant tumors. Am. J. Cancer Res. 2020 10 8 2226 2241 32905441
    [Google Scholar]
  68. Zhang J. Zeng Y. Xing Y. Li X. Zhou L. Hu L. Chin Y.E. Wu M. Myristoylation-mediated phase separation of EZH2 compartmentalizes STAT3 to promote lung cancer growth. Cancer Lett. 2021 516 84 98 10.1016/j.canlet.2021.05.035 34102285
    [Google Scholar]
  69. Grabarz A. Barascu A. Guirouilh-Barbat J. Lopez B.S. Initiation of DNA double strand break repair: signaling and single-stranded resection dictate the choice between homologous recombination, non-homologous end-joining and alternative end-joining. Am. J. Cancer Res. 2012 2 3 249 268 22679557
    [Google Scholar]
  70. Wu Y. Zhou L. Zou Y. Zhang Y. Zhang M. Xu L. Zheng L. He W. Yu K. Li T. Zhang X. Chen Z. Zhang R. Zhou P. Zhang N. Zheng L. Kang T. Disrupting the phase separation of KAT8–IRF1 diminishes PD-L1 expression and promotes antitumor immunity. Nat. Cancer 2023 4 3 382 400 10.1038/s43018‑023‑00522‑1 36894639
    [Google Scholar]
  71. Qin Z. Sun H. Yue M. Pan X. Chen L. Feng X. Yan X. Zhu X. Ji H. Phase separation of EML4–ALK in firing downstream signaling and promoting lung tumorigenesis. Cell Discov. 2021 7 1 33 10.1038/s41421‑021‑00270‑5 33976114
    [Google Scholar]
  72. Lin S.Y. Makino K. Xia W. Matin A. Wen Y. Kwong K.Y. Bourguignon L. Hung M.C. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat. Cell Biol. 2001 3 9 802 808 10.1038/ncb0901‑802 11533659
    [Google Scholar]
  73. Hanada N. Lo H.W. Day C.P. Pan Y. Nakajima Y. Hung M.C. Co‐regulation of B‐Myb expression by E2F1 and EGF receptor. Mol. Carcinog. 2006 45 1 10 17 10.1002/mc.20147 16299810
    [Google Scholar]
  74. Shen M. Zhang R. Jia W. Zhu Z. Zhao L. Huang G. Liu J. RNA-binding protein p54nrb/NONO potentiates nuclear EGFR-mediated tumorigenesis of triple-negative breast cancer. Cell Death Dis. 2022 13 1 42 10.1038/s41419‑021‑04488‑9 35013116
    [Google Scholar]
/content/journals/ccdt/10.2174/0115680096345676241001081051
Loading
Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis
Bentham Science Publishers ; https://doi.org/10.2174/0115680096345676241001081051
/content/journals/ccdt/10.2174/0115680096345676241001081051
/content/journals/ccdt/10.2174/0115680096345676241001081051
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: IGF2BP1 ; liquid-liquid phase separation ; EGFR ; KRT6A ; prognosis ; Lung adenocarcinoma

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