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Int J Mol Sci. 2018 Mar 10;19(3). pii: E803. doi: 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.

Author information

1
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. philipp.strauss@uib.no.
2
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
3
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
4
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. christian.beisland@uib.no.
5
Department of Urology, Haukeland University Hospital, 5021 Bergen, Norway. christian.beisland@uib.no.
6
Spheromics, 81100 Kontiolahti, Finland. andreas.scherer@spheromics.com.
7
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00100 Helsinki, Finland. andreas.scherer@spheromics.com.
8
Department of Clinical Science, University of Bergen, 5021 Bergen, Norway. vegard.lysne@uib.no.
9
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. sabine.leh@helse-bergen.no.
10
Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway. sabine.leh@helse-bergen.no.
11
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. arnar.flatberg@ntnu.no.
12
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. even.koch@uib.no.
13
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway. vidar.beisvag@ntnu.no.
14
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. lea.landolt@uib.no.
15
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway. trude.skogstrand@uib.no.
16
Department of Biomedicine, University of Bergen, 5021 Bergen, Norway. trude.skogstrand@uib.no.
17
Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. oystein.eikrem@uib.no.
18
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway. oystein.eikrem@uib.no.

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.

KEYWORDS:

clear cell renal cell carcinoma/ccRCC; formalin-fixed paraffin-embedded/FFPE; miR-155; microRNA/miRNA; next generation sequencing/NGS

PMID:
29534467
PMCID:
PMC5877664
DOI:
10.3390/ijms19030803
[Indexed for MEDLINE]
Free PMC Article

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