miRNA profiling of small intestinal neuroendocrine tumors defines novel molecular subtypes and identifies miR-375 as a biomarker of patient survival

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Yvonne ArvidssonOla Nilsson

Abstract

The aim of this study was to define the miRNA profile of small intestinal neuroendocrine tumors and to search for novel molecular subgroups and prognostic biomarkers. miRNA profiling was conducted on 42 tumors from 37 patients who underwent surgery for small intestinal neuroendocrine tumors. Unsupervised hierarchical clustering analysis of miRNA profiles identified two groups of tumor metastases, denoted cluster M1 and M2. The smaller cluster M1 was associated with shorter overall survival and contained tumors with higher grade (WHO grade G2/3) and multiple chromosomal gains including gain of chromosome 14. Tumors of cluster M1 had elevated expression of miR-1246 and miR-663a, and reduced levels of miR-488-3p. Pathway analysis predicted Wnt signaling to be the most significantly altered signaling pathway between clusters M1 and M2. Analysis of miRNA expression in relation to tumor proliferation rate showed significant alterations including downregulation of miR-137 and miR-204-5p in tumors with Ki67 index above 3%. Similarly, tumor progression was associated with significant alterations in miRNA expression, e.g. higher expression of miR-95 and miR-210, and lower expression of miR-378a-3p in metastases. Pathway analysis predicte...Continue Reading

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Citations

Aug 6, 2018·Journal of Cellular Physiology·Alireza MafiZatollah Asemi
Jan 8, 2019·Endocrine-related Cancer·Aura D Herrera-MartínezRichard A Feelders
Feb 8, 2019·Endocrine-related Cancer·Tobias HofvingOla Nilsson
Jul 20, 2018·Endocrine-related Cancer·Nicole PanarelliNeil Renwick
Aug 25, 2019·Journal of Clinical Medicine·Claudia von ArxSalvatore Tafuto
Jun 13, 2020·Frontiers in Molecular Biosciences·Simone DetassisMichela Alessandra Denti
Mar 22, 2020·Oncogenesis·Tanupriya Contractor, Chris R Harris
Jan 30, 2021·BMC Cancer·Tobias HofvingYvonne Arvidsson
Jun 3, 2021·Genes·Lilla KrokkerHenriett Butz
Jul 3, 2021·Non-coding RNA·Alexandra KorotaevaAlexander Karpukhin

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Datasets Mentioned

BETA
GSE103317

Methods Mentioned

BETA
biopsies
light microscopy
Feature Extraction
PCR
biopsy
nuclear translocation

Software Mentioned

LIMMA
TargetScan Human
Feature Extraction
Partek Flow
R

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