Please use this identifier to cite or link to this item: https://doi.org/10.14814/phy2.13305
Title: Clear Cell Renal Cell Carcinoma is linked to Epithelial-to-Mesenchymal Transition and to Fibrosis
Authors: Landolt, L
Eikrem, Ø
Strauss, P
Scherer, A
Lovett, D.H
Beisland, C
Finne, K
Osman, T
Ibrahim, M.M
Gausdal, G
Ahmed, L
Lorens, J.B
Thiery, J.P
Tan, T.Z 
Sekulic, M
Marti, H.-P
Keywords: microRNA 34a
transcriptome
axl receptor tyrosine kinase
beta glucuronidase
Klotho protein
matrix metalloproteinase 14
microRNA
MIRN34 microRNA, human
MMP14 protein, human
oncoprotein
protein tyrosine kinase
adult
Article
AXL gene
bioinformatics
clinical article
disease assessment
epithelial mesenchymal transition
epithelial mesenchymal transition score
female
fibrosis
gene
gene expression assay
histopathology
human
human tissue
immunohistochemistry
kidney biopsy
kidney carcinoma
KL gene
liquid chromatography-mass spectrometry
male
middle aged
MMP14 gene
mRNA expression assay
next generation sequencing
proteomics
quality control
radical nephrectomy
RNA extraction
RNA library
RNA sequence
RNA structure
aged
fibrosis
gene expression regulation
genetics
kidney
kidney tumor
metabolism
pathology
renal cell carcinoma
Adult
Aged
Carcinoma, Renal Cell
Epithelial-Mesenchymal Transition
Female
Fibrosis
Gene Expression Regulation, Neoplastic
Glucuronidase
Humans
Kidney
Kidney Neoplasms
Male
Matrix Metalloproteinase 14
MicroRNAs
Middle Aged
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Issue Date: 2017
Citation: Landolt, L, Eikrem, Ø, Strauss, P, Scherer, A, Lovett, D.H, Beisland, C, Finne, K, Osman, T, Ibrahim, M.M, Gausdal, G, Ahmed, L, Lorens, J.B, Thiery, J.P, Tan, T.Z, Sekulic, M, Marti, H.-P (2017). Clear Cell Renal Cell Carcinoma is linked to Epithelial-to-Mesenchymal Transition and to Fibrosis. Physiological Reports 5 (11) : e13305. ScholarBank@NUS Repository. https://doi.org/10.14814/phy2.13305
Rights: Attribution 4.0 International
Abstract: Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC. RNA sequencing libraries were generated using Illumina TruSeq® Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC. Gene expression analysis showed augmented abundance of AXL and MMP14, as well as down-regulated expression of KL (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets MMP14 and AXL. Survival analysis based on a subset of genes from our list EMT-related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Source Title: Physiological Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/178671
ISSN: 205817X
DOI: 10.14814/phy2.13305
Rights: Attribution 4.0 International
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