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Identification of necroptosis-associated mRNA biomarkers in kidney clear cell carcinoma

Xiaobo Zhang1, Qiaoying Jin1, Gafang Cheng1

  • 1Cuiying Biomedical Research Center, The Second Hospital & Clinical Medicine School, Lanzhou University, Lanzhou, China.

Frontiers in Immunology
|September 19, 2025
PubMed
Abstract

Insights

This study identifies new necroptosis-associated biomarkers, CASP8 and TRPM7, for kidney clear cell carcinoma (KIRC). A novel prognostic model improves survival prediction and suggests doxorubicin as a potential treatment for KIRC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Kidney clear cell carcinoma (KIRC) presents high mortality due to genomic heterogeneity and treatment resistance.
  • Necroptosis pathway alterations are implicated in KIRC progression, but previous studies used limited gene sets.
  • Identifying novel biomarkers is crucial for improving KIRC diagnosis and treatment strategies.

Purpose of the Study:

  • To identify and validate novel necroptosis-associated genes as biomarkers for KIRC.
  • To develop and assess a prognostic model for KIRC patient survival.
  • To explore potential therapeutic strategies and experimental models for KIRC.

Main Methods:

  • Comprehensive screening of necroptosis-associated genes in KIRC.
  • Gene expression analysis and validation of core biomarkers.
  • Development and performance evaluation of a 5-year survival prognostic model.
  • Analysis of tumor immune microenvironment and drug sensitivity.
  • Identification of suitable cell lines for in vitro experimental translation.

Main Results:

  • Nine core biomarkers were screened, with CASP8 and TRPM7 identified as novel potential biomarkers.
  • The developed prognostic model demonstrated superior predictive performance for 5-year survival (AUC 0.77-0.89).
  • High-risk patients exhibited pronounced immune responses and immunosuppressive tumor microenvironments.
  • Doxorubicin was identified as a promising therapeutic agent for KIRC.
  • BFTC909 and CAL54 cell lines were suitable for in vitro studies, highlighting CASP8, PGAM5, and CPT2.

Conclusions:

  • This study provides novel necroptosis-associated biomarkers and a validated prognostic model for KIRC.
  • Findings offer insights into KIRC's immune microenvironment and potential therapeutic targets.
  • The results support the development of precision immunotherapy strategies for KIRC.
Keywords:
KIRCbiomarkersimmune microenvironmentnecroptosisprognostictherapeutic target

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