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Published on: July 21, 2017
Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Advanced Non-Small Cell Lung Cancer after Neoadjuvant
Tereza Losmanova1, Philipp Zens1,2, Amina Scherz3
1Institute of Pathology, University of Bern, 3008 Bern, Switzerland.
Abstract:
In recent years autophagy has attracted the attention of researchers from many medical fields, including cancer research, and certain anti-macroautophagy drugs in combination with cytotoxic or targeted therapies have entered clinical trials. In the present study, we focused on a less explored subtype of autophagy, i.e., chaperone-mediated autophagy (CMA), with the key proteins LAMP2A and HSPA8 (HSC70), and their immunohistochemical evaluation with previously extensively validated antibodies. We were interested in whether the marker expression is influenced by the antecedent therapy, and its correlation with survival on a cohort of patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and matched primary resected tumors. In concordance with our previous study, we did not find any intratumoral heterogeneity, nor correlation between the two parameters, nor correlation between the markers and any included pathological parameters. Surprisingly, the expression of both markers was also independent to tumor response or administered neoadjuvant treatment. In the survival analysis, the results were only significant for LAMP2A, where higher levels were associated with longer 5-year overall survival and disease-free survival for the mixed group of adenocarcinomas and squamous cell carcinomas (p < 0.0001 and p = 0.0019 respectively) as well as the squamous cell carcinoma subgroup (p = 0.0001 and p = 0.0001 respectively). LAMP2A was also an independent prognostic marker in univariate and multivariate analysis.
Insights
Chaperone-mediated autophagy (CMA) markers LAMP2A and HSC70 were evaluated in non-small cell lung cancer (NSCLC). Higher LAMP2A expression correlated with improved survival in NSCLC patients, suggesting its prognostic value.
Area of Science:
- Cellular Biology
- Oncology
- Molecular Medicine
Background:
- Autophagy, a cellular degradation process, is increasingly recognized for its role in cancer.
- Chaperone-mediated autophagy (CMA), a less-studied subtype, involves LAMP2A and HSPA8 (HSC70).
- Understanding CMA's role in non-small cell lung cancer (NSCLC) is crucial for therapeutic development.
Purpose of the Study:
- To investigate the immunohistochemical expression of LAMP2A and HSPA8 in NSCLC.
- To assess the influence of neoadjuvant therapy on CMA marker expression.
- To determine the correlation of CMA markers with clinicopathological parameters and patient survival.
Main Methods:
- Immunohistochemical evaluation of LAMP2A and HSPA8 using validated antibodies.
- Analysis of marker expression in relation to antecedent therapy and pathological parameters.
- Survival analysis (overall and disease-free) in NSCLC patients.
Main Results:
- No intratumoral heterogeneity or correlation between LAMP2A and HSPA8 expression.
- Marker expression was independent of antecedent therapy, tumor response, and pathological parameters.
- Elevated LAMP2A levels significantly correlated with longer 5-year overall and disease-free survival in NSCLC, particularly in squamous cell carcinoma.
Conclusions:
- LAMP2A is a potential independent prognostic marker for NSCLC patients.
- CMA marker expression is not significantly affected by neoadjuvant therapy in this cohort.
- Further research into LAMP2A's role could inform NSCLC treatment strategies.
