Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas.

Details

Serval ID
serval:BIB_C61C86E9CF8D
Type
Article: article from journal or magazin.
Collection
Publications
Title
Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas.
Journal
Oncotarget
Author(s)
Adams O., Dislich B., Berezowska S., Schläfli A.M., Seiler C.A., Kröll D., Tschan M.P., Langer R.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
28/06/2016
Peer-reviewed
Oui
Volume
7
Number
26
Pages
39241-39255
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Esophageal adenocarcinomas (EAC) are aggressive tumors with considerable rates of chemoresistance. Autophagy is a lysosome-dependent degradation process, characterized by the formation of vesicles called autophagosomes, and has been implicated in cancer. Protein light chain 3 B (LC3B) and p62 are associated with autophagosomal membranes and degraded. We aimed to assess the impact of basal autophagy on EAC. In EAC cell lines, an increase in LC3B and p62 was observed with increasing concentrations of the autophagy inhibitor chloroquine, which indicates functional basal autophagy. LC3B and p62 immunohistochemistry was performed on primary resected EAC. High LC3B and p62 expression was associated with earlier tumor stages (p < 0.05). High nuclear and cytoplasmic p62 staining were associated with a better prognosis (p = 0.006; p = 0.028). Various combinations of p62 expression with or without LC3B expression identified different prognostic groups. Tumors with low total p62 (p = 0.007) or low LC3B/low p62 expression had the worst outcome (p = 0.007; p = 0.005). A combination score of dot-like/cytoplasmic p62 and nuclear p62 staining was an independent prognostic parameter (p = 0.033; HR = 0.6). This study highlights the potential significance of basal autophagy in EAC biology. Tumors with low LC3B and p62 expression show the most aggressive behavior and may be candidates for autophagy regulating therapeutics.
Keywords
Adenocarcinoma/diagnosis, Adenocarcinoma/metabolism, Adult, Aged, Aged, 80 and over, Autophagy, Biomarkers, Tumor/metabolism, Esophageal Neoplasms/diagnosis, Esophageal Neoplasms/metabolism, Female, Humans, Lysosomes/chemistry, Male, Microtubule-Associated Proteins/metabolism, Middle Aged, Prognosis, RNA-Binding Proteins/metabolism, Treatment Outcome, LC3B, Pathology Section, autophagy, esophageal adenocarcinoma, p62
Pubmed
Web of science
Open Access
Yes
Create date
29/06/2020 12:02
Last modification date
30/06/2020 6:26
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