Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Department of Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Pathol Int. 2022 Oct;72(10):496-505. doi: 10.1111/pin.13262. Epub 2022 Aug 3.
Overexpression of OCIAD2 in lung adenocarcinoma has already been reported in several research articles, but the molecular mechanism involved remains unknown. Promoter CpG methylation is a representative form of epigenetic gene regulation, and a considerable number of tumor suppressor genes show hypermethylation in many cancers. In contrast, promoter CpG hypomethylation causes oncogene overexpression, resulting in carcinogenesis and malignant progression. In the present study, we investigated the CpG methylation and expression status of OCIAD2 using tumor tissues and adjacent normal tissues from seven cases of lung adenocarcinoma. We also examined the relationship between CpG methylation status and outcome in 58 patients with adenocarcinoma. Pyrosequencing showed that CpG sites in OCIAD2 promoter regions were more frequently demethylated in tumor tissues than in adjacent normal tissues, and reverse transcription-quantitative polymerase chain reaction revealed overexpression of OCIAD2 in lung adenocarcinoma. There was a correlation between OCIAD2 CpG demethylation and the level of mRNA expression, and statistical analysis showed that CpG hypomethylation of OCIAD2 was associated with poor outcomes. Our results suggest that overexpression of OCIAD2 might be caused mainly by CpG hypomethylation and that OCIAD2 methylation status might be a useful prognostic indicator in lung adenocarcinoma.
OCIAD2 在肺腺癌中的过表达已在几项研究中报道，但涉及的分子机制尚不清楚。启动子 CpG 甲基化是表观遗传基因调控的一种代表性形式，许多肿瘤抑制基因在许多癌症中表现出过度甲基化。相比之下，启动子 CpG 低甲基化导致癌基因过表达，导致癌变和恶性进展。在本研究中，我们使用来自 7 例肺腺癌的肿瘤组织和相邻正常组织研究了 OCIAD2 的 CpG 甲基化和表达状态。我们还检查了 58 例腺癌患者中 CpG 甲基化状态与结局的关系。焦磷酸测序显示，OCIAD2 启动子区域的 CpG 位点在肿瘤组织中比在相邻正常组织中更频繁地去甲基化，逆转录定量聚合酶链反应显示 OCIAD2 在肺腺癌中过表达。OCIAD2 CpG 去甲基化与 mRNA 表达水平之间存在相关性，统计分析显示 OCIAD2 的 CpG 低甲基化与不良预后相关。我们的结果表明，OCIAD2 的过表达可能主要是由 CpG 低甲基化引起的，OCIAD2 甲基化状态可能是肺腺癌的一个有用的预后指标。
