ArticleScientific reports2017
Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 61 citations in OpenAlex.
- Integrative oxidative stress-disulfidptosis analysis identifiesFrontiers in molecular biosciences · 2026Article
- AI-driven multimodal algorithm predicts immunotherapy and targeted therapy outcomes in clear cell renal cell carcinoma.Cell reports. Medicine · 2025Article
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- OGT/HIF-2α axis promotes the progression of clear cell renal cell carcinoma and regulates its sensitivity to ferroptosis.iScience · 2023Article
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- Investigating the Role ofInternational journal of molecular sciences · 2023Article
- A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma.Frontiers in immunology · 2023Article
- GABPA-activated TGFBR2 transcription inhibits aggressiveness but is epigenetically erased by oncometabolites in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Comprehensive analysis of FRAS1/FREM family as potential biomarkers and therapeutic targets in renal clear cell carcinoma.Frontiers in pharmacology · 2022Article
- Identification of ST3GAL5 as a prognostic biomarker correlating with CD8Frontiers in immunology · 2022Article
- PYCR1 regulates glutamine metabolism to construct an immunosuppressive microenvironment for the progression of clear cell renal cell carcinoma.American journal of cancer research · 2022Article
- Multi-Omics Analysis of the Prognosis and Biological Function for TRPV Channel Family in Clear Cell Renal Cell Carcinoma.Frontiers in immunology · 2022Article
- Multi-omics analysis of intra-tumoural and inter-tumoural heterogeneity in pancreatic ductal adenocarcinoma.Clinical and translational medicine · 2022Article
- Key sunitinib-related biomarkers for renal cell carcinoma.Cancer medicine · 2021Article
- Alternative splicing associated with cancer stemness in kidney renal clear cell carcinoma.BMC cancer · 2021Article
- SPOP-PTEN-SUFU axis promotes progression of clear cell renal cell carcinoma via activating SHH and WNT pathway.Cell death discovery · 2021Article
- Article
- Genomic Instability Promotes the Progression of Clear Cell Renal Cell Carcinoma Through Influencing the Immune Microenvironment.Frontiers in genetics · 2021Article
- Identifying Hypoxia Characteristics to Stratify Prognosis and Assess the Tumor Immune Microenvironment in Renal Cell Carcinoma.Frontiers in genetics · 2021Article
- An eleven metabolic gene signature-based prognostic model for clear cell renal cell carcinoma.Aging · 2020Article
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Authors and funding
15 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clear cell renal cell carcinoma (ccRCC) has been previously classified into putative discrete prognostic subtypes by gene expression profiling. To investigate the robustness of these proposed subtype classifications, we evaluated 12 public datasets, together with a new dataset of 265 ccRCC gene expression profiles. Consensus clustering showed unstable subtype and principal component analysis (PCA) showed a continuous spectrum both within and between datasets. Considering the lack of discrete delineation and continuous spectrum observed, we developed a continuous quantitative prognosis score (Continuous Linear Enhanced Assessment of RCC, or CLEAR score). Prognostic performance was evaluated in independent cohorts from The Cancer Genome Atlas (TCGA) (n = 414) and EMBL-EBI (n = 53), CLEAR score demonstrated both superior prognostic estimates and inverse correlation with anti-angiogenic tyrosine-kinase inhibition in comparison to previously proposed discrete subtyping classifications. Inverse correlation with high-dose interleukin-2 outcomes was also observed for the CLEAR score. Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were associated with the CLEAR score. Application of the CLEAR score to independent expression profiling of intratumoral ccRCC regions demonstrated that average intertumoral heterogeneity exceeded intratumoral expression heterogeneity. Wider investigation of cancer biology using continuous approaches may yield insights into tumor heterogeneity; single cell analysis may provide a key foundation for this approach.
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