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Oncotarget. 2015 Apr 30;6(12):10521-31.

Integrated genomic analysis identifies subclasses and prognosis signatures of kidney cancer.

Author information

1
Institute of Molecular Health Sciences, ETH Zurich, 8093 Zurich, Switzerland.

Abstract

PURPOSE:

To define robust miRNA-based molecular classifiers for human clear cell renal cell carcinoma (ccRCC) subgrouping and prognostication.

EXPERIMENTAL DESIGN:

Multidimensional data of over 500 clear cell renal cell carcinoma (ccRCC) patients were retrieved from The Cancer Genome Atlas (TCGA) archive. Data analysis was based on a novel computational approach that selectively considers patients with extreme expression values of miRNAs to detect survival-associated molecular signatures.

RESULTS:

Our in silico analysis unveiled a novel ccRCC-specific 5-miRNA (miR-10b, miR-21, miR-143, miR-183, and miR-192) signature able, when combined with information from conventional TNM staging and the age of the patient, to prognosticate ccRCC outcome more accurately than known ccRCC miRNA signatures or TNM staging alone. Furthermore, our approach revealed the existence of 6 distinct subgroups of ccRCC characterized by discrete differences in overall survival, tumor stage, and mutational spectra in key ccRCC tumor suppressor genes. It also demonstrated that BAP1 mutations correlate with tumor progression rather than overall survival.

CONCLUSION:

Integrated analysis of multidimensional data from the TCGA archive allowed to draw a portrait of distinct molecular subclasses of human ccRCC and to define signatures for prognosticating disease outcome. Together, these results offer new prospects for more accurate stratification and prognostication of ccRCC.

KEYWORDS:

TCGA; cancer; clear-cell renal cell carcinoma; miRNA; prognosis

PMID:
25826081
PMCID:
PMC4496372
DOI:
10.18632/oncotarget.3294
[Indexed for MEDLINE]
Free PMC Article

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