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Int. J. Mol. Sci. 2018, 19(3), 803; https://doi.org/10.3390/ijms19030803

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.
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)
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Abstract

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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