ArticleTranslational andrology and urology2025
High intratumoral heterogeneity in clear cell renal cell carcinoma is associated with reduced immune response and survival.
Article in Translational andrology and urology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Decoding the Sphingolipid Landscape of Clear Cell Renal Cell Carcinoma: A Single-Cell-Guided Prognostic Model Built With 101 Machine Learning.Human mutation · 2026Article
- Multidimensional tumor heterogeneity and its role in therapeutic resistance.Frontiers in immunology · 2026Review
- The Role of Homologous Recombination Deficiency (HRD) in Renal Cell Carcinoma (RCC): Biology, Biomarkers, and Therapeutic Opportunities.Current oncology (Toronto, Ont.) · 2025Review
- Spatial immunoprofiling of retroperitoneal leiomyosarcomas reveals intratumoral heterogeneity in immune cell infiltration, checkpoint molecule expression, and tertiary lymphoid structures.Annals of medicine · 2025Article
- Case Report: Late simultaneous metastasis of renal clear cell carcinoma to the ampulla and breast.Frontiers in oncology · 2025Article
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Authors and funding
6 authors.
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Abstract
Background: Clear cell renal cell carcinoma (ccRCC) exhibits high intratumor heterogeneity (ITH), which drives progression, metastasis, and treatment resistance. Nevertheless, clinically applicable tools for predicting patient prognosis based on ITH remain unavailable, and the association between ITH and immune cell response is a matter of debate. The objective of this study was to establish ITH as a clinically relevant biomarker capable of predicting outcomes and informing treatment strategies in ccRCC. Methods: The Bioconductor R package Maftools was used to analyze somatic variants of ccRCC from The Cancer Genome Atlas (TCGA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to estimate immune cell compositions. A mutant-allele tumor heterogeneity (MATH) algorithm was used to measure ITH, and we explored its correlation with clinical parameters and immune cell response. Results: Our analysis revealed that lower MATH values were significantly associated with increased infiltration of activated dendritic cells (P=0.048) and reduced levels of immunosuppressive regulatory T cells (Tregs; P=0.02), suggesting enhanced antitumor immunity in less heterogeneous tumors. Conversely, high MATH values correlated with worse overall survival and a suppressed immune microenvironment. These findings support the potential of MATH as a stratification biomarker for ccRCC patients, helping identify those who may benefit from immunotherapy or targeted therapies. Conclusions: High MATH value correlates with worse survival and decreased immune response in ccRCC patients.
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