Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7EBFC3818D19
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades.
Journal
Cancers
Author(s)
Simbolo M., Bilotta M., Mafficini A., Luchini C., Furlan D., Inzani F., Petrone G., Bonvissuto D., La Rosa S., Schinzari G., Bianchi A., Rossi E., Menghi R., Giuliante F., Boccia S., Scarpa A., Rindi G.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
23/04/2021
Peer-reviewed
Oui
Volume
13
Number
9
Pages
2054
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability.
Keywords
Ki67, LINE-1, NET, gene expression profiling, grade, neuroendocrine tumor, pancreas
Pubmed
Web of science
Open Access
Yes
Create date
03/05/2021 7:50
Last modification date
29/05/2021 6:31
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