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Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives: Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma

1
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway
2
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
3
Department of Urology, Haukeland University Hospital, 5021 Bergen, Norway
4
Spheromics, 81100 Kontiolahti, Finland
5
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00100 Helsinki, Finland
6
Department of Clinical Science, University of Bergen, 5021 Bergen, Norway
7
Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway
8
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway
9
Department of Biomedicine, University of Bergen, 5021 Bergen, Norway
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(3), 803; https://doi.org/10.3390/ijms19030803
Received: 15 December 2017 / Revised: 3 March 2018 / Accepted: 3 March 2018 / Published: 10 March 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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. View Full-Text
Keywords: microRNA/miRNA; miR-155; clear cell renal cell carcinoma/ccRCC; formalin-fixed paraffin-embedded/FFPE; next generation sequencing/NGS microRNA/miRNA; miR-155; clear cell renal cell carcinoma/ccRCC; formalin-fixed paraffin-embedded/FFPE; next generation sequencing/NGS
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Strauss, P.; Marti, H.-P.; Beisland, C.; Scherer, A.; Lysne, V.; Leh, S.; Flatberg, A.; Koch, E.; Beisvag, V.; Landolt, L.; Skogstrand, T.; Eikrem, Ø. Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives: Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma. Int. J. Mol. Sci. 2018, 19, 803.

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