Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n= 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. In a comparison of tumour vs. normal, 182 miRNAs were found with significant differential expression; miR-155 was of particular interest as it classified all ccRCC samples correctly and correlated well with tumour size (R² = 0.83); miR-155 also predicted poor survival with hazard ratios of 2.58 and 1.81 in two different TCGA (The Cancer Genome Atlas) datasets in a univariate model. However, in a multivariate Cox regression analysis including age, sex, cancer stage and histological grade, miR-155 was not a statistically significant survival predictor. In conclusion, formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA-sequencing material. Our results further support a role for miR-155 as a promising cancer classifier and potentially as a therapeutic target in ccRCC that merits further investigation.
International journal of molecular sciences. 2018 Mar 10*** epublish ***
Philipp Strauss, Hans-Peter Marti, Christian Beisland, Andreas Scherer, Vegard Lysne, Sabine Leh, Arnar Flatberg, Even Koch, Vidar Beisvag, Lea Landolt, Trude Skogstrand, Øystein Eikrem
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. ., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. ., Spheromics, 81100 Kontiolahti, Finland. ., Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. ., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. ., Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. ., Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. ., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. ., Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway. ., Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. .