Evaluation of a microRNA-based Risk Classifier Predicting Cancer-Specific Survival in Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava

Abstract

Introduction: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCCIVC) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier - containing miR-21, miR-126 and miR-221 expression - which significantly predicted cancer-specific survival (CSS) of ccRCCIVC patients. Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCCIVC, we measured expression levels of miR-21, miR-126 and miR-221 by qRT-PCR. Prognostic impact of clinicopathological parameters and miR expression were investigated via univariate and multivariate cox regression. Referring to the previously established risk classifier, we performed Kaplan Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at time of surgery, development of metastasis during follow-up, and cancer-related death. In Kaplan Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCCIVC according to CSS. Conclusion: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCCIVC cohort.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Markus Krebs was funded by a personal grant from Else-Kroener-Foundation (Else Kroener Integrative Clinician Scientist College for Translational Immunology, University Hospital Wuerzburg, Germany).

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the local Ethics Committees (Regensburg: Nr. 08/108, Wuerzburg: Nr. 136/08).

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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