MicroRNA expression profiles in molecular subtypes of clear-cell renal cell carcinoma are associated with clinical outcome and repression of specific mRNA targets.

Autor: Verbiest A; Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.; Department of Oncology, Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium., Van Hoef V; Bioinformatics Expertise Center, VIB, Leuven, Belgium., Rodriguez-Antona C; Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain., García-Donas J; Oncology Unit, HM Hospitales-Centro Integral Oncologico HM Clara Campal, Madrid, Spain.; Spanish Oncology Genitourinary Group, Madrid, Spain., Graña-Castro O; Bioinformatics Unit, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain., Albersen M; Department of Urology, University Hospitals Leuven, Leuven, Belgium., Baldewijns M; Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Laenen A; Biostatistics and Statistical Bioinformatics Center, KU Leuven, Leuven, Belgium., Roussel E; Department of Urology, University Hospitals Leuven, Leuven, Belgium., Schöffski P; Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.; Department of Oncology, Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium., Wozniak A; Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.; Department of Oncology, Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium., Caruso S; Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France., Couchy G; Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France., Zucman-Rossi J; Inserm, UMR-1162, Génomique fonctionnelle des tumeurs solides, IUH, Paris, France., Beuselinck B; Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.; Department of Oncology, Laboratory of Experimental Oncology, KU Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Sep 11; Vol. 15 (9), pp. e0238809. Date of Electronic Publication: 2020 Sep 11 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0238809
Abstrakt: Clear-cell renal cell carcinomas (ccRCC) can be divided into four transcriptomic subtypes, two of which have a favorable and two an unfavorable prognosis. To assess mechanisms driving these subtypes, we investigated their miRNA expression patterns. miRNAs are master regulators of mRNAs, that are widely deregulated in cancer. Unsupervised clustering in our dataset (n = 128) and The Cancer Genome Atlas (TCGA) validation set identified two distinct miRNA clusters that overlapped with the transcriptomic subtypes, underscoring the validity of these subtypes on a multi-omics level and suggesting a driving role for miRNAs. Discriminatory miRNAs for the favorable subtypes repressed epithelial-to-mesenchymal transition, based on gene set enrichment analysis and target-mRNA expression levels. Strikingly, throughout the entire dataset, miRNAs associated with favorable subtypes were also associated with longer overall survival after diagnosis, and miRNAs associated with unfavorable subtypes with shorter overall survival (Pearson r = -0.54, p<0.0001). These findings indicate a general shift in miRNA expression between more and less aggressive tumors. This adds to current literature, which usually suggests only a small subset of miRNAs as markers of aggressive disease. In conclusion, this study reveals distinct mRNA expression patterns underlying transcriptomic ccRCC-subtypes, whereby miRNAs associated with favorable subtypes counteract epithelial-to-mesenchymal transition. There is a general shift in miRNA expression in ccRCC, between more and less aggressive tumors.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Benoit Beuselinck received consultancy fees from Amgen, Ipsen, Pfizer and Novartis and institutional research grants from Bristol-Myers Squibb and Ipsen. Patrick Schöffski has received consultancy fees as well as institutional research grants from Merck and Exelixis. The other authors have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje