Skip to content
2000
Volume 28, Issue 17
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073235329231005094452
2024-11-07
2025-12-21

  • From This Site

    /content/journals/cchts/10.2174/0113862073235329231005094452
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. WarburgO. The metabolism of carcinoma cells.J. Cancer Res.192591481633
     [Google Scholar]
  2. Vander HeidenM.G. CantleyL.C. ThompsonC.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation.Science200932459301029103310.1126/science.1160809 19460998
     [Google Scholar]
  3. GhoshS. BlumenthalH.J. DavidsonE. RosemanS. Glucosamine metabolism.J. Biol. Chem.196023551265127310.1016/S0021‑9258(18)69397‑4 13827775
     [Google Scholar]
  4. DenzelM.S. StormN.J. GutschmidtA. BaddiR. HinzeY. JaroschE. SommerT. HoppeT. AntebiA. Hexosamine pathway metabolites enhance protein quality control and prolong life.Cell201415661167117810.1016/j.cell.2014.01.061 24630720
     [Google Scholar]
  5. KroefV. RuegenbergS. HornM. AllmerothK. EbertL. BozkusS. MietheS. EllingU. SchermerB. BaumannU. DenzelM.S. GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway.eLife202211e6922310.7554/eLife.69223 35229715
     [Google Scholar]
  6. de QueirozR.M. OliveiraI.A. PivaB. Bouchuid CatãoF. da Costa RodriguesB. da Costa PascoalA. DiazB.L. TodeschiniA.R. CaarlsM.B. DiasW.B. Hexosamine biosynthetic pathway and glycosylation regulate cell migration in melanoma cells.Front. Oncol.2019911610.3389/fonc.2019.00116 30891426
     [Google Scholar]
  7. LeeJ.B. PyoK.H. KimH.R. Role and function of o-glcnacylation in cancer.Cancers20211321536510.3390/cancers13215365 34771527
     [Google Scholar]
  8. HuangH. WangY. HuangT. WangL. LiuY. WuQ. YuA. ShiM. WangX. LiW. ZhangJ. LiuY. FOXA2 inhibits doxorubicin-induced apoptosis via transcriptionally activating HBP rate-limiting enzyme GFPT1 in HCC cells.J. Physiol. Biochem.202177462563810.1007/s13105‑021‑00829‑6 34291417
     [Google Scholar]
  9. ChaoD. AriakeK. SatoS. OhtsukaH. TakadateT. IshidaM. MasudaK. MaedaS. MiuraT. MitachiK. YuX. FujishimaF. MizumaM. NakagawaK. MorikawaT. KameiT. UnnoM. 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.20214569010.3892/or.2021.8041 33846782
     [Google Scholar]
  10. LiuW. JiangK. WangJ. MeiT. ZhaoM. HuangD. Upregulation of GNPNAT1 predicts poor prognosis and correlates with immune infiltration in lung adenocarcinoma.Front. Mol. Biosci.2021860575410.3389/fmolb.2021.605754 33842535
     [Google Scholar]
  11. AkellaN.M. CirakuL. ReginatoM.J. Fueling the fire: Emerging role of the hexosamine biosynthetic pathway in cancer.BMC Biol.20191715210.1186/s12915‑019‑0671‑3 31272438
     [Google Scholar]
  12. OkiT. YamazakiK. KuromitsuJ. OkadaM. TanakaI. cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse.Genomics199957222723410.1006/geno.1999.5785 10198162
     [Google Scholar]
  13. ArreolaR. ValderramaB. MoranteM.L. HorjalesE. Two mammalian glucosamine-6-phosphate deaminases: A structural and genetic study.FEBS Lett.20035511-3637010.1016/S0014‑5793(03)00896‑2 12965206
     [Google Scholar]
  14. SimpsonN.E. TryndyakV.P. BelandF.A. PogribnyI.P. An in vitro investigation of metabolically sensitive biomarkers in breast cancer progression.Breast Cancer Res. Treat.2012133395996810.1007/s10549‑011‑1871‑x
     [Google Scholar]
  15. DingX. LiuH. YuanY. ZhongQ. ZhongX. Roles of GFPT2 expression levels on the prognosis and tumor microenvironment of colon cancer.Front. Oncol.20221281155910.3389/fonc.2022.811559 35330716
     [Google Scholar]
  16. ZhangL. SunW. RenW. ZhangJ. XuG. Predicting panel of metabolism and immune-related genes for the prognosis of human ovarian cancer.Front. Cell Dev. Biol.20219690542
     [Google Scholar]
  17. ZhangH. JiaY. CooperJ.J. HaleT. ZhangZ. ElbeinS.C. 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.2004892748755
     [Google Scholar]
  18. KimJ. LeeH.M. CaiF. KoB. YangC. LieuE.L. MuhammadN. RhyneS. LiK. HaloulM. GuW. FaubertB. KaushikA.K. CaiL. KasiriS. MarriamU. NhamK. GirardL. WangH. SunX. KimJ. MinnaJ.D. Unsal-KacmazK. DeBerardinisR.J. The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer.Nat. Metab.20202121401141210.1038/s42255‑020‑00316‑0 33257855
     [Google Scholar]
  19. ZhaoH. DenneryP.A. YaoH. Metabolic reprogramming in the pathogenesis of chronic lung diseases, including BPD, COPD, and pulmonary fibrosis.Am. J. Physiol. Lung Cell. Mol. Physiol.20183144L544L54
     [Google Scholar]
  20. YoshiharaK. ShahmoradgoliM. MartínezE. VegesnaR. KimH. Torres-GarciaW. TreviñoV. ShenH. LairdP.W. LevineD.A. CarterS.L. GetzG. Stemke-HaleK. MillsG.B. VerhaakR.G.W. Inferring tumour purity and stromal and immune cell admixture from expression data.Nat. Commun.201341261210.1038/ncomms3612 24113773
     [Google Scholar]
  21. LiuY. WuY. ZhangP. XuC. LiuZ. HeC. LiuY. KangZ. CXCL12 and CD3E as indicators for tumor microenvironment modulation in bladder cancer and their correlations with immune infiltration and molecular subtypes.Front. Oncol.20211163687010.3389/fonc.2021.636870 33747959
     [Google Scholar]
  22. NewmanA.M. LiuC.L. GreenM.R. GentlesA.J. FengW. XuY. HoangC.D. DiehnM. AlizadehA.A. Robust enumeration of cell subsets from tissue expression profiles.Nat. Methods201512545345710.1038/nmeth.3337 25822800
     [Google Scholar]
  23. CristescuR. MoggR. AyersM. AlbrightA. MurphyE. YearleyJ. SherX. LiuX.Q. LuH. NebozhynM. ZhangC. LuncefordJ.K. JoeA. ChengJ. WebberA.L. IbrahimN. PlimackE.R. OttP.A. SeiwertT.Y. RibasA. McClanahanT.K. TomassiniJ.E. LobodaA. KaufmanD. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy.Science20183626411eaar359310.1126/science.aar3593 30309915
     [Google Scholar]
  24. BonnevilleR KrookMA KauttoEA MiyaJ WingMR ChenHZ Landscape of microsatellite instability across 39 cancer types.JCO Precis. Oncol.2017201717.00073
     [Google Scholar]
  25. LaraP.N.Jr RedmanM.W. KellyK. EdelmanM.J. WilliamsonS.K. CrowleyJ.J. GandaraD.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.200826346346710.1200/JCO.2007.13.0344 18202421
     [Google Scholar]
  26. ZhangW. BouchardG. YuA. ShafiqM. JamaliM. ShragerJ.B. AyersK. BakrS. GentlesA.J. DiehnM. QuonA. WestR.B. NairV. van de RijnM. NapelS. PlevritisS.K. GFPT2 -expressing cancer-associated fibroblasts mediate metabolic reprogramming in human lung adenocarcinoma.Cancer Res.201878133445345710.1158/0008‑5472.CAN‑17‑2928 29760045
     [Google Scholar]
  27. McKnightG.L. MudriS.L. MathewesS.L. TraxingerR.R. MarshallS. SheppardP.O. O’HaraP.J. Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase.J. Biol. Chem.199226735252082521210.1016/S0021‑9258(19)74026‑5 1460020
     [Google Scholar]
  28. MattilaJ. KokkiK. HietakangasV. BoutrosM. stem cell intrinsic hexosamine metabolism regulates intestinal adaptation to nutrient content.Dev. Cell2018471112121.e310.1016/j.devcel.2018.08.011 30220570
     [Google Scholar]
  29. MoZ. LiP. CaoZ. ZhangS. A comprehensive pan-cancer analysis of 33 human cancers reveals the immunotherapeutic value of aryl hydrocarbon receptor.Front. Immunol.20211256494810.3389/fimmu.2021.564948 34290693
     [Google Scholar]
  30. Al-MukhH. BaudoinL. BouaboudA. Sanchez-SalgadoJ.L. MaraqaN. KhairM. PagesyP. BismuthG. NiedergangF. IssadT. Lipopolysaccharide Induces GFAT2 Expression to Promote O -Linked β- N -Acetylglucosaminylation and Attenuate Inflammation in Macrophages.J. Immunol.202020592499251010.4049/jimmunol.2000345 32978282
     [Google Scholar]
  31. MasugiY. NishiharaR. HamadaT. SongM. da SilvaA. KosumiK. GuM. ShiY. LiW. LiuL. NevoD. InamuraK. CaoY. LiaoX. NoshoK. ChanA.T. GiannakisM. BassA.J. HodiF.S. FreemanG.J. RodigS.J. FuchsC.S. QianZ.R. NowakJ.A. OginoS. Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer.Cancer Immunol. Res.20175111046105510.1158/2326‑6066.CIR‑17‑0122 29038297
     [Google Scholar]
  32. YangY WangX BaiY FengD LiA TangY Programmed death-ligand 2 (PD-L2) expression in bladder cancer.Urol Oncol.2020386603-e9- e15
     [Google Scholar]
  33. AriafarA. GhaediM. RezaeifardS. ShahriariS. ZeighamiS. GhaderiA. FaghihZ. Clinical relevance and prognostic significance of PD-1/PD-Ls in non-metastatic bladder cancer: A role for PD-L2.Mol. Immunol.2020124354110.1016/j.molimm.2020.05.010 32512320
     [Google Scholar]
  34. VillarinoA.V. KannoY. O’SheaJ.J. Mechanisms and consequences of Jak–STAT signaling in the immune system.Nat. Immunol.201718437438410.1038/ni.3691 28323260
     [Google Scholar]
  35. ZhangY. ZhangH. ZhaoB. Hippo signaling in the immune system.Trends Biochem. Sci.2018432778010.1016/j.tibs.2017.11.009 2924956
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073235329231005094452
Loading
The Prognostic Value and Immunotherapeutic Characteristics of GFPT2 in Pan-cancer
Comb Chem High Throughput Screen 28, 2989 (2025); https://doi.org/10.2174/0113862073235329231005094452
/content/journals/cchts/10.2174/0113862073235329231005094452
/content/journals/cchts/10.2174/0113862073235329231005094452
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): GFPT2; HBP; immune infiltration; oncotherapy; pan-cancer analysis; prognosis

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