The Clinical Influence of Autophagy-Associated Proteins on Human Lung Cancer

Exploitation of autophagy might potentially improve therapeutic strategy. Here, we analyzed the protein expression of autophagy-associated genes including LC3A, LC3B, Beclin-1, p62, and Atg5 in 88–131 primary lung tumors by immunohistochemistry (IHC) on tissue-microarrays (TMAs). Additionally, the DNA methylation pattern of LC3A was investigated by bisulfite sequencing (BS) and methylation-specific-PCR (MSP). It turned out that the higher expression of LC3A protein was associated with adenocarcinoma compared to squamous cell carcinoma of lung (p=0.008), positive staining of LC3B was significantly related to tumor grade (p=0.006), and the protein expression of Beclin-1 was significantly correlated to pN stage (p=0.041). The expression of p62 and Atg5 was however not significantly associated with any clinicopathological parameters. Downregulation of LC3A was related to DNA methylation in lung cancer cell lines, while in primary lung tumor samples, protein expression of LC3A was not significantly correlated with DNA methylation, and the methylation status of LC3A was not related to clinicopathological features. Taken together, our results suggest that autophagy-associated proteins such as LC3A, LC3B, and Beclin-1 might be potential biomarkers for subclassification, differentiation, and local metastasis in primary lung tumor, and epigenetic mechanism is partially responsible for gene silencing of LC3A in lung cancer cell lines.