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Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms

Abstract：

Objective:Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas; however, their prognosis differs significantly upon their proliferative state, which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs. Methods:MiRNA expression profiles of 40 PanNENs were downloaded from Gene Expression Omnibus and were reanalyzed upon tumor grades (discovery cohort). Results of the reanalysis were confirmed by qRT-PCR analysis of five miRNAs on an independent validation cohort of 63 primary PanNEN samples. Cox proportional hazards survival regression models were fit for both univariate and multivariate analysis to determine the miRNAs’ effect on progression-free and overall survival. Results:Nineteen miRNAs displayed differential expression between tumor grades. The altered expression of three out of five chosen miRNAs was successfully validated; hsa-miR-21, hsa-miR-10a and hsa-miR-106b were upregulated in more proliferative PanNENs compared to Grade 1 tumors. In univariate analysis, higher expression of tissue hsa-miR-21, hsa-miR-10a and hsa-miR-106b of primary PanNENs predicted worse progression-free and overall survival; however, multivariate analysis only confirmed the expression of hsa-miR-21 as an independent prognostic factor. Conclusions:The expression of hsa-miR-106b, hsa-miR-10a and especially hsa-miR-21 has prognostic relevance regarding progression-free and overall survival in patients with PanNENs.

journal_name

Eur J Endocrinol

journal_title

European journal of endocrinology

authors

Grolmusz VK,Kövesdi A,Borks K,Igaz P,Patócs A

doi

10.1530/EJE-18-0305

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

219-228

issue

4

eissn

0804-4643

issn

1479-683X

journal_volume

179

pub_type

杂志文章

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