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

Autor: Mario P. Tschan, Anna M. Schläfli, Sabina Berezowska, Ralph A. Schmid, Tereza Losmanová, Magali Humbert, Félice A. Janser, Rupert Langer, Christina Neppl, Igor Tokarchuk
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Oncology
Adult
Male
Aging
medicine.medical_specialty
Lung Neoplasms
Article Subject
Cell
Chaperone-Mediated Autophagy
610 Medicine & health
Kaplan-Meier Estimate
Protein degradation
Biochemistry
Disease-Free Survival
Chaperone-mediated autophagy
Downregulation and upregulation
Internal medicine
Aged
Aged
80 and over
Biomarkers/metabolism
Carcinoma
Squamous Cell/diagnosis
Carcinoma
Squamous Cell/mortality
Carcinoma
Squamous Cell/pathology
Chaperone-Mediated Autophagy/genetics
Female
HSC70 Heat-Shock Proteins/genetics
HSC70 Heat-Shock Proteins/metabolism
Humans
Lung Neoplasms/diagnosis
Lung Neoplasms/mortality
Lung Neoplasms/pathology
Lysosomal-Associated Membrane Protein 2/genetics
Lysosomal-Associated Membrane Protein 2/metabolism
Middle Aged
Prognosis
Proportional Hazards Models
Retrospective Studies
Lysosomal-Associated Membrane Protein 2
medicine
Gene knockdown
Tissue microarray
Lung
QH573-671
business.industry
HSC70 Heat-Shock Proteins
Cell Biology
General Medicine
medicine.anatomical_structure
Carcinoma
Squamous Cell
Immunohistochemistry
570 Life sciences
biology
business
Cytology
Corrigendum
Biomarkers
Research Article
Zdroj: Oxidative Medicine and Cellular Longevity
Losmanová, Tereza; Janser, Félice A.; Humbert, Magali; Tokarchuk, Igor; Schläfli, Anna M.; Neppl, Christina; Schmid, Ralph; Tschan, Mario P.; Langer, Rupert; Berezowska, Sabina (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, 2020, p. 8506572. Hindawi 10.1155/2020/8506572
Oxidative medicine and cellular longevity, vol. 2020, pp. 8506572
Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
ISSN: 1942-0994
1942-0900
DOI: 10.1155/2020/8506572
Popis: 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=0.012andp=0.001) and disease free survival (DFS;p=0.049andp=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.
Databáze: OpenAIRE
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