ArticleGenome medicine2022
A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 28 citations in OpenAlex.
- CAIX-targeted PET/CT in the evaluation of clear cell renal cell carcinoma: a head-to-head comparison with [European journal of nuclear medicine and molecular imaging · 2026Trial
- Integrative multi-omics analysis identifies SMIM24 as a favorable prognostic biomarker in clear cell renal cell carcinoma.Functional & integrative genomics · 2026Article
- SUMOylation-Driven Subtype Heterogeneity and Prognostic Biomarkers in Renal Cell Carcinoma.Current issues in molecular biology · 2026Article
- Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Updates on Clinical Trials and Molecular Characteristics of Locally Advanced and Oligometastatic Renal Cell Carcinoma.International journal of molecular sciences · 2026Review
- Novel nested conformal prediction analysis to unravel complexity in patient subtyping.Frontiers in artificial intelligence · 2026Article
- Construction and validation of renal cell carcinoma tumor cell differentiation-related prognostic classification (RCC-TCDC): an integrated bioinformatic analysis and clinical study.Annals of medicine · 2025Article
- Urogenital Cancers: New Molecular and Translational Aspects on Carcinogenesis and Treatments.Biomedicines · 2025Article
- Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.Nature cancer · 2025Article
- A multi-omics features-based approach integrating immunogenicity and inflammation enhances immunotherapy benefit in clear cell renal cell carcinoma.Frontiers in cell and developmental biology · 2025Article
- TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: a multicohort study.Journal of the National Cancer Center · 2024Article
- CTCF-activated FUCA1 functions as a tumor suppressor by promoting autophagy flux and serum α-L-fucosidase serves as a potential biomarker for prognosis in ccRCC.Cancer cell international · 2024Article
- A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma.Biomedicines · 2024Article
- Decoding ecosystem heterogeneity and transcriptional regulation characteristics of multi-subtype renal cell carcinoma.Heliyon · 2024Article
- Bioinformatics in urology - molecular characterization of pathophysiology and response to treatment.Nature reviews. Urology · 2024Review
- Article
- Management of Renal Cell Carcinoma: Promising Biomarkers and the Challenges to Reach the Clinic.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Prognostic value and immune landscapes of immunogenic cell death-associated lncRNAs in lung adenocarcinoma.Scientific reports · 2023Article
- Transcriptional profiles reveal histologic origin and prognosis across 33 The Cancer Genome Atlas tumor types.Translational cancer research · 2023Article
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Authors and funding
28 authors at 12 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRenal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes.
methodsIndividual RCC samples were modeled as linear combination of the main subtypes (clear cell (ccRCC), papillary (pRCC), chromophobe (chRCC)) using computational gene expression deconvolution. The new molecular subtyping was compared with histological classification of RCC using the Cancer Genome Atlas (TCGA) cohort (n = 864; ccRCC: 512; pRCC: 287; chRCC: 65) as well as 92 independent histopathologically well-characterized RCC. Predicted continuous subtypes were correlated to cancer-specific survival (CSS) in the TCGA cohort and validated in 242 independent RCC. Association with treatment-related progression-free survival (PFS) was studied in the JAVELIN Renal 101 (n = 726) and IMmotion151 trials (n = 823). CSS and PFS were analyzed using the Kaplan-Meier and Cox regression analysis.
resultsOne hundred seventy-four signature genes enabled reference-free molecular classification of individual RCC. We unambiguously assign tumors to either ccRCC, pRCC, or chRCC and uncover molecularly heterogeneous tumors (e.g., with ccRCC and pRCC features), which are at risk of worse outcome. Assigned proportions of molecular subtype-features significantly correlated with CSS (ccRCC (P = 4.1E - 10), pRCC (P = 6.5E - 10), chRCC (P = 8.6E - 06)) in TCGA. Translation into a numerical RCC-R(isk) score enabled prognosis in TCGA (P = 9.5E - 11). Survival modeling based on the RCC-R score compared to pathological categories was significantly improved (P = 3.6E - 11). The RCC-R score was validated in univariate (P = 3.2E - 05; HR = 3.02, 95% CI: 1.8-5.08) and multivariate analyses including clinicopathological factors (P = 0.018; HR = 2.14, 95% CI: 1.14-4.04). Heterogeneous PD-L1-positive RCC determined by molecular subtyping showed increased PFS with checkpoint inhibition versus sunitinib in the JAVELIN Renal 101 (P = 3.3E - 04; HR = 0.52, 95% CI: 0.36 - 0.75) and IMmotion151 trials (P = 0.047; HR = 0.69, 95% CI: 0.48 - 1). The prediction of PFS significantly benefits from classification into heterogeneous and unambiguous subtypes in both cohorts (P = 0.013 and P = 0.032).
conclusionSwitching from categorical to continuous subtype classification across most frequent RCC subtypes enables outcome prediction and fosters personalized treatment strategies.
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