Institute of Pathology, University Hospital Jena, Friedrich Schiller University Jena, Jena, Germany.
Dis Markers. 2018 Jan 9;2018:8314963. doi: 10.1155/2018/8314963. eCollection 2018.
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 ( = 0.008), positive staining of LC3B was significantly related to tumor grade ( = 0.006), and the protein expression of Beclin-1 was significantly correlated to pN stage ( = 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.
自噬的开发可能有潜力改善治疗策略。在这里，我们通过组织微阵列（TMA）上的免疫组织化学（IHC）分析了包括 LC3A、LC3B、Beclin-1、p62 和 Atg5 在内的自噬相关基因的蛋白表达。此外，还通过亚硫酸氢盐测序（BS）和甲基化特异性 PCR（MSP）研究了 LC3A 的 DNA 甲基化模式。结果表明，LC3A 蛋白的高表达与肺腺癌有关，而与肺鳞癌相比（= 0.008），LC3B 的阳性染色与肿瘤分级显著相关（= 0.006），而 Beclin-1 的蛋白表达与 pN 分期显著相关（= 0.041）。然而，p62 和 Atg5 的表达与任何临床病理参数均无显著相关性。LC3A 的下调与肺癌细胞系中的 DNA 甲基化有关，而在原发性肺肿瘤样本中，LC3A 的蛋白表达与 DNA 甲基化无显著相关性，并且 LC3A 的甲基化状态与临床病理特征无关。总之，我们的研究结果表明，LC3A、LC3B 和 Beclin-1 等自噬相关蛋白可能是原发性肺肿瘤亚分类、分化和局部转移的潜在生物标志物，并且表观遗传机制部分负责肺癌细胞系中 LC3A 的基因沉默。
