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Open Access Research article

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

Daniel Vergho1*, Susanne Kneitz2, Andreas Rosenwald3, Charlotte Scherer1, Martin Spahn4, Maximilian Burger1, Hubertus Riedmiller1 and Burkhard Kneitz1

Author Affiliations

1 Department of Urology and Paediatric Urology, Julius-Maximilians-University Medical Centre of Würzburg, Würzburg, Germany

2 Physiological Chemistry I, Biocentre, University of Würzburg, Würzburg, Germany

3 Department of Pathology, University of Würzburg, Würzburg, Germany

4 Department of Urology, University of Bern, Bern, Switzerland

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BMC Cancer 2014, 14:25  doi:10.1186/1471-2407-14-25

Published: 15 January 2014

Abstract

Background

Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs.

Methods

Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC).

Results

RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease.

Conclusions

A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Keywords:
Renal cell carcinoma; RCC; Kidney cancer; miRNA; miR-21; miR-126; Prognosis; Profiling; Biomarker; Tumour markers