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image of The Prognostic Value and Immunotherapeutic Characteristics of GFPT2 in Pan-cancer

Abstract

Purpose

The purpose of this study is to investigate the underlying relationship of diagnosis and therapy between glutamine-fructose-6-phosphate transaminase 2 (GFPT2) and various cancers.

Methods

The Cancer Genome Atlas (TCGA) database was utilized to get gene expression RNAseq and clinical data for 33 tumors. The immunotherapeutic cohorts, including GSE35640, GSE78220, GSE67501, GSE181815, and IMvigor210, were derived from the Gene Expression Omnibus database (GEO) and a previously released article. Differential expression analysis of GFPT2 was performed using several clinical factors, and prognostic analysis was performed using Cox proportional hazard regression. In addition, the Cell type Identification By Estimating Relative Subsets Of RNA transcripts (CIBERSORT) and the Estimation of STromal and Immune cells in MAlignant Tumor tissues utilizing Expression data (ESTIMATE) algorithms were used to investigate the connection between GFPT2 and the tumor microenvironment. This approach additionally incorporated dynamic immunological indicators, such as tumor mutational burden (TMB) and microsatellite instability (MSI). In addition, a correlation between GFPT2 expression and the effectiveness of anticancer drugs was plotted for discussion.

Results

GFPT2 expression significantly differed in 11 out of 33 cancers. Although the distinct correlation between GFPT2 expression and clinical parameters had no wide distribution in pan-cancer, it demonstrated the potential prognostic validity of gene expression. GFPT2 demonstrated a strong correlation with immune infiltration, immune modulators, and immune-related biomarkers. Furthermore, a variance analysis demonstrated a significant relationship between GFPT2 and the efficacy of immunotherapy. In addition, GFPT2 was associated with increased sensitivity of drugs such as Olaparib and Lenvatinib and decreased sensitivity of drugs such as Nilotinib.

Conclusion

Collectively, GFPT2 is potentially useful as a biomarker for prognostic prediction and immune infiltration in a variety of malignancies, and could lead to exciting new approaches to personalized oncotherapy.

© 2024 Bentham Science Publishers
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2024-11-07
2025-03-01

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References

  1. Warburg O. The metabolism of carcinoma cells. J Cancer Res. 1925 9 148 1633
    [Google Scholar]
  2. Vander Heiden M.G. Cantley L.C. Thompson C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009 324 5930 1029 1033 10.1126/science.1160809 19460998
    [Google Scholar]
  3. Ghosh S. Blumenthal H.J. Davidson E. Roseman S. Glucosamine metabolism. J. Biol. Chem. 1960 235 5 1265 1273 10.1016/S0021‑9258(18)69397‑4 13827775
    [Google Scholar]
  4. Denzel M.S. Storm N.J. Gutschmidt A. Baddi R. Hinze Y. Jarosch E. Sommer T. Hoppe T. Antebi A. Hexosamine pathway metabolites enhance protein quality control and prolong life. Cell 2014 156 6 1167 1178 10.1016/j.cell.2014.01.061 24630720
    [Google Scholar]
  5. Kroef V. Ruegenberg S. Horn M. Allmeroth K. Ebert L. Bozkus S. Miethe S. Elling U. Schermer B. Baumann U. Denzel M.S. GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway. eLife 2022 11 e69223 10.7554/eLife.69223 35229715
    [Google Scholar]
  6. de Queiroz R.M. Oliveira I.A. Piva B. Bouchuid Catão F. da Costa Rodrigues B. da Costa Pascoal A. Diaz B.L. Todeschini A.R. Caarls M.B. Dias W.B. Hexosamine biosynthetic pathway and glycosylation regulate cell migration in melanoma cells. Front. Oncol. 2019 9 116 10.3389/fonc.2019.00116 30891426
    [Google Scholar]
  7. Lee J.B. Pyo K.H. Kim H.R. Role and function of o-glcnacylation in cancer. Cancers 2021 13 21 5365 10.3390/cancers13215365 34771527
    [Google Scholar]
  8. Huang H. Wang Y. Huang T. Wang L. Liu Y. Wu Q. Yu A. Shi M. Wang X. Li W. Zhang J. Liu Y. FOXA2 inhibits doxorubicin-induced apoptosis via transcriptionally activating HBP rate-limiting enzyme GFPT1 in HCC cells. J. Physiol. Biochem. 2021 77 4 625 638 10.1007/s13105‑021‑00829‑6 34291417
    [Google Scholar]
  9. Chao D. Ariake K. Sato S. Ohtsuka H. Takadate T. Ishida M. Masuda K. Maeda S. Miura T. Mitachi K. Yu X. Fujishima F. Mizuma M. Nakagawa K. Morikawa T. Kamei T. Unno M. Stomatin‑like protein 2 induces metastasis by regulating the expression of a rate‑limiting enzyme of the hexosamine biosynthetic pathway in pancreatic cancer. Oncol. Rep. 2021 45 6 90 10.3892/or.2021.8041 33846782
    [Google Scholar]
  10. Liu W. Jiang K. Wang J. Mei T. Zhao M. Huang D. Upregulation of GNPNAT1 predicts poor prognosis and correlates with immune infiltration in lung adenocarcinoma. Front. Mol. Biosci. 2021 8 605754 10.3389/fmolb.2021.605754 33842535
    [Google Scholar]
  11. Akella N.M. Ciraku L. Reginato M.J. Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer. BMC Biol. 2019 17 1 52 10.1186/s12915‑019‑0671‑3 31272438
    [Google Scholar]
  12. Oki T. Yamazaki K. Kuromitsu J. Okada M. Tanaka I. cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse. Genomics 1999 57 2 227 234 10.1006/geno.1999.5785 10198162
    [Google Scholar]
  13. Arreola R. Valderrama B. Morante M.L. Horjales E. Two mammalian glucosamine-6-phosphate deaminases: A structural and genetic study. FEBS Lett. 2003 551 1-3 63 70 10.1016/S0014‑5793(03)00896‑2 12965206
    [Google Scholar]
  14. Simpson NE Tryndyak VP Beland FA Pogribny IP An in vitro investigation of metabolically sensitive biomarkers in breast cancer progression. Breast Cancer Res Treat 2012 133 3 959 968 10.1007/s10549‑011‑1871‑x
    [Google Scholar]
  15. Ding X. Liu H. Yuan Y. Zhong Q. Zhong X. Roles of GFPT2 expression levels on the prognosis and tumor microenvironment of colon cancer. Front. Oncol. 2022 12 811559 10.3389/fonc.2022.811559 35330716
    [Google Scholar]
  16. Zhang L Sun W Ren W Zhang J Xu G. Predicting panel of metabolism and immune-related genes for the prognosis of human ovarian cancer. Front Cell Dev Biol. 2021 9 690542
    [Google Scholar]
  17. Zhang H Jia Y Cooper JJ Hale T Zhang Z Elbein SC. Common variants in glutamine:fructose-6-phosphate amidotransferase 2 (GFPT2) gene are associated with type 2 diabetes, diabetic nephropathy, and increased GFPT2 mRNA levels. J Clin Endocrinol Metab. 2004 89 2 748 755
    [Google Scholar]
  18. Kim J. Lee H.M. Cai F. Ko B. Yang C. Lieu E.L. Muhammad N. Rhyne S. Li K. Haloul M. Gu W. Faubert B. Kaushik A.K. Cai L. Kasiri S. Marriam U. Nham K. Girard L. Wang H. Sun X. Kim J. Minna J.D. Unsal-Kacmaz K. DeBerardinis R.J. The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer. Nat. Metab. 2020 2 12 1401 1412 10.1038/s42255‑020‑00316‑0 33257855
    [Google Scholar]
  19. Zhao H Dennery PA Yao H Metabolic reprogramming in the pathogenesis of chronic lung diseases, including BPD, COPD, and pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2018 314 4 L544 L54
    [Google Scholar]
  20. Yoshihara K. Shahmoradgoli M. Martínez E. Vegesna R. Kim H. Torres-Garcia W. Treviño V. Shen H. Laird P.W. Levine D.A. Carter S.L. Getz G. Stemke-Hale K. Mills G.B. Verhaak R.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 2013 4 1 2612 10.1038/ncomms3612 24113773
    [Google Scholar]
  21. Liu Y. Wu Y. Zhang P. Xu C. Liu Z. He C. Liu Y. Kang Z. CXCL12 and CD3E as Indicators for Tumor Microenvironment Modulation in Bladder Cancer and Their Correlations With Immune Infiltration and Molecular Subtypes. Front. Oncol. 2021 11 636870 10.3389/fonc.2021.636870 33747959
    [Google Scholar]
  22. Newman A.M. Liu C.L. Green M.R. Gentles A.J. Feng W. Xu Y. Hoang C.D. Diehn M. Alizadeh A.A. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 2015 12 5 453 457 10.1038/nmeth.3337 25822800
    [Google Scholar]
  23. Cristescu R. Mogg R. Ayers M. Albright A. Murphy E. Yearley J. Sher X. Liu X.Q. Lu H. Nebozhyn M. Zhang C. Lunceford J.K. Joe A. Cheng J. Webber A.L. Ibrahim N. Plimack E.R. Ott P.A. Seiwert T.Y. Ribas A. McClanahan T.K. Tomassini J.E. Loboda A. Kaufman D. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy. Science 2018 362 6411 eaar3593 10.1126/science.aar3593 30309915
    [Google Scholar]
  24. Bonneville R Krook MA Kautto EA Miya J Wing MR Chen HZ Landscape of microsatellite instability across 39 cancer types. JCO Precis Oncol. 2017 2017 17.00073
    [Google Scholar]
  25. Lara P.N. Jr Redman M.W. Kelly K. Edelman M.J. Williamson S.K. Crowley J.J. Gandara D.R. Disease control rate at 8 weeks predicts clinical benefit in advanced non-small-cell lung cancer: results from Southwest Oncology Group randomized trials. J. Clin. Oncol. 2008 26 3 463 467 10.1200/JCO.2007.13.0344 18202421
    [Google Scholar]
  26. Zhang W. Bouchard G. Yu A. Shafiq M. Jamali M. Shrager J.B. Ayers K. Bakr S. Gentles A.J. Diehn M. Quon A. West R.B. Nair V. van de Rijn M. Napel S. Plevritis S.K. GFPT2 -expressing cancer-associated fibroblasts mediate metabolic reprogramming in human lung adenocarcinoma. Cancer Res. 2018 78 13 3445 3457 10.1158/0008‑5472.CAN‑17‑2928 29760045
    [Google Scholar]
  27. McKnight G.L. Mudri S.L. Mathewes S.L. Traxinger R.R. Marshall S. Sheppard P.O. O’Hara P.J. Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase. J. Biol. Chem. 1992 267 35 25208 25212 10.1016/S0021‑9258(19)74026‑5 1460020
    [Google Scholar]
  28. Mattila J. Kokki K. Hietakangas V. Boutros M. stem cell intrinsic hexosamine metabolism regulates intestinal adaptation to nutrient content. Dev. Cell 2018 47 1 112 121.e3 10.1016/j.devcel.2018.08.011 30220570
    [Google Scholar]
  29. Mo Z. Li P. Cao Z. Zhang S. A comprehensive pan-cancer analysis of 33 human cancers reveals the immunotherapeutic value of aryl hydrocarbon receptor. Front. Immunol. 2021 12 564948 10.3389/fimmu.2021.564948 34290693
    [Google Scholar]
  30. Al-Mukh H. Baudoin L. Bouaboud A. Sanchez-Salgado J.L. Maraqa N. Khair M. Pagesy P. Bismuth G. Niedergang F. Issad T. Lipopolysaccharide Induces GFAT2 Expression to Promote O -Linked β- N -Acetylglucosaminylation and Attenuate Inflammation in Macrophages. J. Immunol. 2020 205 9 2499 2510 10.4049/jimmunol.2000345 32978282
    [Google Scholar]
  31. Masugi Y. Nishihara R. Hamada T. Song M. da Silva A. Kosumi K. Gu M. Shi Y. Li W. Liu L. Nevo D. Inamura K. Cao Y. Liao X. Nosho K. Chan A.T. Giannakis M. Bass A.J. Hodi F.S. Freeman G.J. Rodig S.J. Fuchs C.S. Qian Z.R. Nowak J.A. Ogino S. Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer. Cancer Immunol. Res. 2017 5 11 1046 1055 10.1158/2326‑6066.CIR‑17‑0122 29038297
    [Google Scholar]
  32. Yang Y Wang X Bai Y Feng D Li A Tang Y Programmed death-ligand 2 (PD-L2) expression in bladder cancer. Urol Oncol. 2020 38 6 603 e9- e15
    [Google Scholar]
  33. Ariafar A. Ghaedi M. Rezaeifard S. Shahriari S. Zeighami S. Ghaderi A. Faghih Z. Clinical relevance and prognostic significance of PD-1/PD-Ls in non-metastatic bladder cancer: A role for PD-L2. Mol. Immunol. 2020 124 35 41 10.1016/j.molimm.2020.05.010 32512320
    [Google Scholar]
  34. Villarino A.V. Kanno Y. O’Shea J.J. Mechanisms and consequences of Jak–STAT signaling in the immune system. Nat. Immunol. 2017 18 4 374 384 10.1038/ni.3691 28323260
    [Google Scholar]
  35. Zhang Y. Zhang H. Zhao B. Hippo signaling in the immune system. Trends Biochem. Sci. 2018 43 2 77 80 10.1016/j.tibs.2017.11.009 29249569
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073235329231005094452
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The Prognostic Value and Immunotherapeutic Characteristics of GFPT2 in Pan-cancer
Bentham Science Publishers ; https://doi.org/10.2174/0113862073235329231005094452
/content/journals/cchts/10.2174/0113862073235329231005094452
/content/journals/cchts/10.2174/0113862073235329231005094452
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  • Article Type:     Research Article
Keywords: pan-cancer analysis ; immune infiltration ; oncotherapy ; HBP ; prognosis ; GFPT2

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