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

• Published in: Disease markers 2018-01, Vol.2018 (2018), p.1-9
• Main Authors: Theis, Bernhard, Nenkov, Miljana, Ma, Yunxia, Schnitzler, Kai Leonie, Chen, Yuan, Petersen, Iver
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Aged; Autophagy; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Beclin-1 - genetics; Beclin-1 - metabolism; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biotechnology; Bisulfite; Cancer; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Deoxyribonucleic acid; DNA; DNA Methylation; DNA microarrays; DNA sequencing; Epigenetic inheritance; Exploitation; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene silencing; Genes; Genetic engineering; Health aspects; Humans; Immunohistochemistry; Lung cancer; Lung carcinoma; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphatic Metastasis; Male; Metastases; Methylation; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Phagocytosis; Protein expression; Proteins; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Squamous cell carcinoma; Sulfites; Tissue Array Analysis; Tumor cell lines; Tumors
• ISSN: 0278-0240; 1875-8630
• DOI: 10.1155/2018/8314963

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.