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

(1) Background: 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-21-5p, miR-126-3p and miR-221-3p expression-which significantly predicted the cancer-specific survival (CSS) of ccRCCIVC patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCCIVC, we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable 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. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the 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. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCCIVC cohort.

Cancers. 2023 Mar 26*** epublish ***

Mischa J Kotlyar, Markus Krebs, Antonio Giovanni Solimando, André Marquardt, Maximilian Burger, Hubert Kübler, Ralf Bargou, Susanne Kneitz, Wolfgang Otto, Johannes Breyer, Daniel C Vergho, Burkhard Kneitz, Charis Kalogirou

Department of Urology and Pediatric Urology, University Hospital Würzburg, 97080 Würzburg, Germany., Guido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, 70124 Bari, Italy., Department of Pathology, Klinikum Stuttgart, 70174 Stuttgart, Germany., Department of Urology, Caritas St. Josef, University of Regensburg Medical Center, 93053 Regensburg, Germany., Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, 97080 Würzburg, Germany., Physiological Chemistry I, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97074 Würzburg, Germany.