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

Joint Authors

Losmanová, Tereza
Janser, Félice A.
Humbert, Magali
Tokarchuk, Igor
Schläfli, Anna M.
Neppl, Christina
Schmid, Ralph A.
Tschan, Mario P.
Langer, Rupert
Berezowska, Sabina

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-09-22

Country of Publication

Egypt

No. of Pages

12

Main Subjects

Biology

Abstract EN

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.

American Psychological Association (APA)

Losmanová, Tereza& Janser, Félice A.& Humbert, Magali& Tokarchuk, Igor& Schläfli, Anna M.& Neppl, Christina…[et al.]. 2020. Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1205626

Modern Language Association (MLA)

Losmanová, Tereza…[et al.]. Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1205626

American Medical Association (AMA)

Losmanová, Tereza& Janser, Félice A.& Humbert, Magali& Tokarchuk, Igor& Schläfli, Anna M.& Neppl, Christina…[et al.]. Chaperone-Mediated Autophagy Markers LAMP2A and HSC70 Are Independent Adverse Prognostic Markers in Primary Resected Squamous Cell Carcinomas of the Lung. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1205626

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1205626