Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_E70EE8341A34
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung.
Journal
Oxidative medicine and cellular longevity
Author(s)
Losmanová T., Janser F.A., Humbert M., Tokarchuk I., Schläfli A.M., Neppl C., Schmid R.A., Tschan M.P., Langer R., Berezowska S.
ISSN
1942-0994 (Electronic)
ISSN-L
1942-0994
Publication state
Published
Issued date
21/09/2020
Peer-reviewed
Oui
Volume
2020
Pages
8506572
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
LAMP2A and HSC70 are crucial players in chaperone-mediated autophagy (CMA), a targeted, lysosome-dependent protein degradation pathway. Elevated LAMP2A levels, indicative of increased CMA activity, are observed in several malignancies, and CMA downregulation may be exploited therapeutically. We evaluated the impact of LAMP2A and HSC70 in pulmonary squamous cell carcinomas (pSQCC). Antibodies were validated by knockdown and overexpression experiments using three different cell lines. Expression levels in tissue were analyzed by immunohistochemistry in a cohort of 336 consecutive pSQCC using tissue microarrays. There was no significant correlation between the two markers among each other and no association with pathological parameters (TNM categories, grading). However, both high LAMP2A and HSC70 expression were associated with worse outcome, including overall survival (OS; p = 0.012 and p = 0.001) and disease free survival (DFS; p = 0.049 and p = 0.036). In multivariate analysis, both markers and a combination of them were independent adverse prognostic factors for OS (LAMP2Ahigh: HR = 2.059; p < 0.001; HSC70high: HR = 1.987; p < 0.001; LAMP2Ahigh/HSC70high: HR = 1.529; p < 0.001) and DFS (LAMP2Ahigh: HR = 1.709; p = 0.004; HSC70high: HR = 1.484; p = 0.027; LAMP2Ahigh/HSC70high: HR = 1.342, p < 0.001). The negative prognostic impact of high LAMP2A and HSC70 and their variable expression in pSQCC may justify the use of these proteins as potential biomarkers for future CMA-inhibiting therapies.
Pubmed
Web of science
Open Access
Yes
Create date
09/10/2020 12:10
Last modification date
02/03/2021 6:26
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