Multi-omics profiling Profiling nominates Nominates caspaseCaspase-6 (CASP6) as a clinically actionablecCandidate prognostic Prognostic signaturebBiomarker in kidney Kidney renal Renal clear Clear cell Cell carcinomaCarcinoma

Authors

  • Shuai Ma Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical University, Anyuan Road, Chengde 067000, China
  • Tian Zhang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Neinan Street, Beijing 100700, China
  • Yang Liu Hebei Province Key Laboratory of Nerve Injury and Repair, School of Basic Medical Sciences, Chengde Medical University, Anyuan Road, Chengde 067000, China
  • Yueying Xu Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical University, Anyuan Road, Chengde 067000, China
  • Jianjun Cheng Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical University, Anyuan Road, Chengde 067000, China
  • Chunying Zhao
  • Yu Cao Chengde Medical University image/svg+xml , Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical University, Anyuan Road, Chengde 067000, China
  • Chunhan Qiao Hebei Province Key Laboratory of Research and Development of Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical University, Anyuan Road, Chengde 067000, China

DOI:

https://doi.org/10.11113/mjfas.v22n6.4691

Keywords:

caspase, anticancer, prognostic potential, CASP6, kidney renal clear cell carcinoma

Abstract

Caspase (CASP) family members have been proposedare frequently employed as pharmacodynamic biomarkers for monitoringto evaluate anticancer therapeutic responses, yet their prognostic relevance across malignancies remains incompletely characterizedunderexplored. The present investigation systematically assessed the prognostic potentialclinical utility of seven proapoptosis-associated caspase genes (CASP2/3/6/7/8/9/10) across pan-cancer cohorts usingas pan-cancer prognostic indicators. Iintegrative analysis of TIMER2.0, PrognoScan, and GEPIA2 databases. The screening identified CASP6 and CASP9 as candidate survival-associated geneskey survival predictors:; elevated CASP6 expression correlated with favorable outcomes in kidney renal clear cell carcinoma (KIRC) and colon adenocarcinoma, while high CASP9 levels were associated with improvedpredicted ameliorative survival in kidney renal papillary cell carcinoma (KIRP). TIMER2.0 immune events analysis revealed CASP6-associated distinct immune microenvironment remodeling in KIRC, characterized by coordinated infiltration withof B cells, CD4+ T cells, and myeloid populations. UALCAN methylation profiling demonstrated tumor-specific promoter hypermethylation of CASP6 in KIRC and CASP9 in KIRP, which is strongly correlated with transcriptional downregulation. cBioPortal analysis identified missense mutations (CASP6- E16G/K238R in colon adenocarcinoma; CASP9- S133F in KIRP) classified as variants of uncertain significance. Through multi-omics integrationvalidation, CASP6 emerged as a candidaterobust transcriptional biomarker forin KIRC, with expression levels stratifyingshowing potential associations with therapeutic response probabilities. These findings establishedsuggest that caspase expression signature may serve as complementary tools for prognostic stratification in renal malignancies.

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Published

30-10-2026

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Vol. 22 No. 5 (2026): September-October

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Copyright (c) 2026 Shuai Ma, Tian Zhang, Yang Liu, Yueying Xu, Jianjun Cheng, Chunying Zhao, Yu Cao, Chunhan Qiao

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How to Cite

Multi-omics profiling Profiling nominates Nominates caspaseCaspase-6 (CASP6) as a clinically actionablecCandidate prognostic Prognostic signaturebBiomarker in kidney Kidney renal Renal clear Clear cell Cell carcinomaCarcinoma. (2026). Malaysian Journal of Fundamental and Applied Sciences, 22(5), 1055-1067. https://doi.org/10.11113/mjfas.v22n6.4691