Oncotarget

Research Papers:

Integrated genomic analysis identifies subclasses and prognosis signatures of kidney cancer

Yann Christinat _ and Wilhelm Krek

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Oncotarget. 2015; 6:10521-10531. https://doi.org/10.18632/oncotarget.3294

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Abstract

Yann Christinat1, Wilhelm Krek1

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

Correspondence to:

Wilhelm Krek, e-mail: [email protected]

Keywords: miRNA, cancer, clear-cell renal cell carcinoma, prognosis, TCGA

Received: January 13, 2015     Accepted: February 08, 2015     Published: March 24, 2015

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.


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