Differential expression analysis of clear cell renal cell carcinomas in The Cancer Genome Atlas distinguishes an aggressive subset enriched with chromosomes 7 and 12 gains
- 14 March 2020
- journal article
- research article
- Published by Wiley in Histopathology
- Vol. 76 (7), 950-958
- https://doi.org/10.1111/his.14104
Abstract
Aims The Cancer Genome Atlas (TCGA) provides an integrated resource for investigating the genetic, phenotypic and clinical characteristics of cancer. In this study, we aimed to define distinct subsets of clear cell renal cell carcinoma (ccRCC) through differential expression and principal component analyses. Methods and results We used DESeq2 to examine the expression profiles of 472 cases in TCGA. After a process of segregation and regrouping, we compared the mutation and copy number variation landscapes to discern two major clusters: Cluster 1, composed mostly of classic ccRCC, and Cluster 2, which was associated with gains at chromosomes 7 and 12. Geneset enrichment analysis disclosed that Cluster 2 tumours were enriched in genes involving epithelial‐ mesenchymal transition. Histologically, Cluster 2 tumours frequently exhibited cell elongation or spindling. Patients with Cluster 2 tumours or tumours harboring chromosome 7 or 12 gain had a significantly heightened cumulative incidence of mortality. We then employed fluorescence in situ hybridisation with probes against chromosomes 7 and 12 in a cohort of 119 cases of ccRCC from our institute for validation. Chromosomes 7 and 12 gains were associated with lower survival rates in both univariate and multivariate analyses. Conclusions Our study demonstrates that genetic data obtained through appropriate molecular methodologies can be a useful adjunct to help predict prognosis. It also provides an example of exploring TCGA to extract meaningful information that can eventually contribute to precision medicine.Keywords
This publication has 13 references indexed in Scilit:
- GenVisR: Genomic Visualizations in RBioinformatics, 2016
- Clear Cell-Papillary Renal Cell Carcinoma of the Kidney Not Associated With End-stage Renal DiseaseThe American Journal of Surgical Pathology, 2015
- Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2Genome Biology, 2014
- Integrated molecular analysis of clear-cell renal cell carcinomaNature Genetics, 2013
- Comprehensive molecular characterization of clear cell renal cell carcinomaNature, 2013
- Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor BiologyEuropean Urology, 2012
- Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival PatternsGenes & Cancer, 2010
- Chromosomal abnormalities of clear cell renal cell carcinoma: Frequent gain of chromosome 7Pathology International, 2009
- Cytogenetic Profile Predicts Prognosis of Patients With Clear Cell Renal Cell CarcinomaJournal of Clinical Oncology, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005