Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Cancer Drug Targets
  4. Volume 25, Issue 3
  5. Article
Volume 25, Issue 3
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

It remains controversial whether the current subtypes of kidney renal papillary cell carcinoma (KIRP) can be used to predict the prognosis independently.

Objective

This observational study aimed to identify a risk signature based on necroptotic process-related genes (NPRGs) in KIRP.

Methods

In the training cohort, LASSO regression was applied to construct the risk signature from 158 NPRGs, followed by the analysis of Overall Survival (OS) using the Kaplan-Meier method. The signature accuracy was evaluated by the Receiver Operating Characteristic (ROC) curve, which was further validated by the test cohort. Wilcoxon test was used to compare the expressions of immune-related genes, neoantigen genes, and immune infiltration between different risk groups, while the correlation test was performed between NPRGs expressions and drug sensitivity. Gene set enrichment analysis was used to investigate the NPRGs' signature’s biological functions.

Results

We finally screened out 4-NPRGs (BIRC3, CAMK2B, PYGM, and TRADD) for constructing the risk signature with the area under the ROC curve (AUC) reaching about 0.8. The risk score could be used as an independent OS predictor. Consistent with the enriched signaling, the NPRGs signature was found to be closely associated with neoantigen, immune cell infiltration, and immune-related functions. Based on NPRGs expressions, we also predicted multiple drugs potentially sensitive or resistant to treatment.

Conclusion

The novel 4-NPRGs risk signature can predict the prognosis, immune infiltration, and therapeutic sensitivity of KIRP.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096286503240321040556
2024-04-08
2025-01-18

  • From This Site

    /content/journals/ccdt/10.2174/0115680096286503240321040556
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MarchettiA. RoselliniM. MollicaV. RizzoA. TassinariE. NuvolaG. CimadamoreA. SantoniM. FiorentinoM. MontironiR. MassariF. The molecular characteristics of non-clear cell renal cell carcinoma: What’s the story morning glory?Int. J. Mol. Sci.20212212623710.3390/ijms2212623734207825
     [Google Scholar]
  2. XiongS. ZhuW. LiX. YuY. YangK. ZhangL. MiY. LiX. ZhouL. Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: Evidence from a systematic review and meta-analysis.Transl. Androl. Urol.20211083255326610.21037/tau‑21‑32934532250
     [Google Scholar]
  3. MugliaV.F. PrandoA. Renal cell carcinoma: Histological classification and correlation with imaging findings.Radiol. Bras.201548316617410.1590/0100‑3984.2013.192726185343
     [Google Scholar]
  4. BrodziakA. SobczukP. BartnikE. FiedorowiczM. PortaC. SzczylikC. CzarneckaA.M. Drug resistance in papillary RCC: From putative mechanisms to clinical practicalities.Nat. Rev. Urol.2019161165567310.1038/s41585‑019‑0233‑z31602010
     [Google Scholar]
  5. LiuY. LiuT. LeiT. ZhangD. DuS. GiraniL. QiD. LinC. TongR. WangY. RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review).Int. J. Mol. Med.201944377178610.3892/ijmm.2019.424431198981
     [Google Scholar]
  6. SeoJ. NamY.W. KimS. OhD.B. SongJ. Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators.Exp. Mol. Med.20215361007101710.1038/s12276‑021‑00634‑734075202
     [Google Scholar]
  7. ZhanC. HuangM. YangX. HouJ. MLKL: Functions beyond serving as the executioner of necroptosis.Theranostics202111104759476910.7150/thno.5407233754026
     [Google Scholar]
  8. GongY. FanZ. LuoG. YangC. HuangQ. FanK. ChengH. JinK. NiQ. YuX. LiuC. The role of necroptosis in cancer biology and therapy.Mol. Cancer201918110010.1186/s12943‑019‑1029‑831122251
     [Google Scholar]
  9. NajafovA. ChenH. YuanJ. Necroptosis and cancer.Trends Cancer20173429430110.1016/j.trecan.2017.03.00228451648
     [Google Scholar]
  10. HernandezC. HuebenerP. SchwabeR.F. Damage-associated molecular patterns in cancer: A double-edged sword.Oncogene201635465931594110.1038/onc.2016.10427086930
     [Google Scholar]
  11. YatimN. SaklaniJ.H. OrozcoS. SchulzO. da SilvaB.R. e SousaR.C. GreenD.R. OberstA. AlbertM.L. RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8 + T cells.Science2015350625832833410.1126/science.aad039526405229
     [Google Scholar]
  12. ChenW. LinW. WuL. XuA. LiuC. HuangP. A novel prognostic predictor of immune microenvironment and therapeutic response in kidney renal clear cell carcinoma based on necroptosis-related gene signature.Int. J. Med. Sci.202219237739210.7150/ijms.6906035165523
     [Google Scholar]
  13. LinW. ChenW. ZhongJ. UekiH. XuA. WatanabeM. ArakiM. LiuC. NasuY. HuangP. Identification of MICALL2 as a novel prognostic biomarker correlating with inflammation and T cell exhaustion of kidney renal clear cell carcinoma.J. Cancer20221341214122810.7150/jca.6692235281853
     [Google Scholar]
  14. SituY. XuQ. DengL. ZhuY. GaoR. LeiL. ShaoZ. System analysis of VEGFA in renal cell carcinoma: The expression, prognosis, gene regulation network and regulation targets.Int. J. Biol. Markers20213719010134870494
     [Google Scholar]
  15. XuH. ZhengX. ZhangS. YiX. ZhangT. WeiQ. LiH. AiJ. Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma.Mol. Cancer202120115910.1186/s12943‑021‑01465‑w34872567
     [Google Scholar]
  16. MifflinL. OfengeimD. YuanJ. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nat. Rev. Drug Discov.202019855357110.1038/s41573‑020‑0071‑y32669658
     [Google Scholar]
  17. WuY. DongG. ShengC. Targeting necroptosis in anticancer therapy: Mechanisms and modulators.Acta Pharm. Sin. B20201091601161810.1016/j.apsb.2020.01.00733088682
     [Google Scholar]
  18. DuanY. ZhangD. Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma.J. Cell. Biochem.2020121167268910.1002/jcb.2931431407370
     [Google Scholar]
  19. YangF. ZhaoG. GeL. SongY. HongK. ZhangH. LiuC. HongP. MaL. Identification of a Two-m6A RNA methylation regulator risk signature as an independent prognostic biomarker in papillary renal cell carcinoma by bioinformatic analysis.BioMed Res. Int.2021202111010.1155/2021/458208233628782
     [Google Scholar]
  20. ZhouX. QiuS. JinD. JinK. ZhengX. YangL. WeiQ. Development and validation of an individualized immune-related gene pairs prognostic signature in papillary renal cell carcinoma.Front. Genet.20201156988410.3389/fgene.2020.56988433240321
     [Google Scholar]
  21. FeiH. ChenS. XuC. Construction autophagy-related prognostic risk signature combined with clinicopathological validation analysis for survival prediction of kidney renal papillary cell carcinoma patients.BMC Cancer202121141110.1186/s12885‑021‑08139‑233858375
     [Google Scholar]
  22. GuX. ChenX. ZhuL. SongW. WangA. ChuJ. WangT. JiangP. GeY. Development of an autophagy score signature for predicting overall survival in papillary renal cell carcinoma.Dis. Markers202020201810.1155/2020/886701933273989
     [Google Scholar]
  23. ShiJ. WangK. XiongZ. YuanC. WangC. CaoQ. YuH. MengX. XieK. ChengZ. YangH. ChenK. ZhangX. Impact of inflammation and immunotherapy in renal cell carcinoma (Review).Oncol. Lett.2020205110.3892/ol.2020.1213533014151
     [Google Scholar]
  24. De Vries-BrillandM. Gross-GoupilM. BoughalemE. BeuselinckB. ThibaultC. ChevreauC. LadoireS. BarthelemyP. NegrierS. BorchielliniD. HuillardO. GeoffroisL. GravisG. SaldanaC. VuilleminT.A. SeegersV. EscudierB. RavaudA. AlbigesL. Are immune checkpoint inhibitors (ICI) a valid option for papillary renal cell carcinoma (pRCC)? A multicenter retrospective study.J. Clin. Oncol.201937S758258210.1200/JCO.2019.37.7_suppl.582
     [Google Scholar]
  25. McDermottD.F. LeeJ.L. ZiobroM. SuarezC. LangiewiczP. MatveevV.B. WiechnoP. GafanovR.A. TomczakP. PouliotF. DonskovF. AlekseevB.Y. ShinS.J. BjarnasonG.A. CastellanoD. SilvermanR.K. PeriniR.F. SchlossC. AtkinsM.B. Open-label, single-arm, phase II study of pembrolizumab monotherapy as first-line therapy in patients with advanced non–clear cell renal cell carcinoma.J. Clin. Oncol.20213991029103910.1200/JCO.20.0236533529058
     [Google Scholar]
  26. PykeR.M. MellacheruvuD. DeaS. AbbottC.W. ZhangS.V. PhillipsN.A. HarrisJ. BarthaG. DesaiS. McCloryR. WestJ. SnyderM.P. ChenR. BoyleS.M. Precision neoantigen discovery using large-scale immunopeptidomes and composite modeling of MHC peptide presentation.Mol. Cell. Proteomics20212010011110.1016/j.mcpro.2021.10011134126241
     [Google Scholar]
  27. WaldmanA.D. FritzJ.M. LenardoM.J. A guide to cancer immunotherapy: From T cell basic science to clinical practice.Nat. Rev. Immunol.2020201165166810.1038/s41577‑020‑0306‑532433532
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096286503240321040556
Loading
The Necroptotic Process-related Signature Predicts Immune Infiltration and Drug Sensitivity in Kidney Renal Papillary Cell Carcinoma
Curr. Cancer Drug Targets< 25, 244 (2025); https://doi.org/10.2174/0115680096286503240321040556
/content/journals/ccdt/10.2174/0115680096286503240321040556
/content/journals/ccdt/10.2174/0115680096286503240321040556
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): drug sensitivity; gene signature; immune infiltration; kidney renal papillary cell carcinoma; Necroptosis; 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