International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, 110, Taipei, Taiwan.
AIBioMed Research Group, Taipei Medical University, Taipei, 110, Taiwan.
Funct Integr Genomics. 2023 Jul 31;23(3):256. doi: 10.1007/s10142-023-01185-y.
Non-small cell lung cancer (NSCLC) is the most prevalent histological type of lung cancer and the leading cause of death globally. Patients with NSCLC have a poor prognosis for various factors, and a late diagnosis is one of them. The DNA methylation of CpG island sequences found in the promoter regions of tumor suppressor genes has recently received attention as a potential biomarker of human cancer. In this study, we report DNA methylation changes of the adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), which belongs to the ATP cassette transporter family in NSCLC patients. Our results demonstrate that ABCG1 is hyper-methylation in NSCLC samples, and these changes are negatively correlated to gene and protein expression. Furthermore, the expression of the ABCG1 gene is significantly associated with the survival time of lung adenocarcinoma (LUAD) patients; however, it did not show a correlation to overall survival (OS) of lung squamous cell carcinoma (LUSC) patients. Notably, we found ABCG1 methylation status at locus cg20214535 is strongly associated with the survival time and consistently observed hyper-methylation in LUAD samples. This novel finding suggests ABCG1 is a potential candidate for targeted therapy in lung cancer via this specific probe. In addition, we illustrate the protein-protein interaction (PPI) of ABCG1 with other proteins and the strong communication of ABCG1 with immune cells.
非小细胞肺癌（NSCLC）是最常见的肺癌组织学类型，也是全球死亡的主要原因。由于多种因素，NSCLC 患者的预后较差，其中之一是诊断较晚。最近，人们关注肿瘤抑制基因启动子区域内 CpG 岛序列的 DNA 甲基化作为人类癌症的潜在生物标志物。在本研究中，我们报告了属于 ATP 盒转运体家族的三磷酸腺苷（ATP）结合盒转运蛋白 G1（ABCG1）在 NSCLC 患者中的 DNA 甲基化变化。我们的结果表明，ABCG1 在 NSCLC 样本中呈高甲基化，这些变化与基因和蛋白表达呈负相关。此外，ABCG1 基因的表达与肺腺癌（LUAD）患者的生存时间显著相关；然而，它与肺鳞状细胞癌（LUSC）患者的总生存（OS）无相关性。值得注意的是，我们发现位于 cg20214535 位的 ABCG1 甲基化状态与生存时间密切相关，并且在 LUAD 样本中一致观察到高甲基化。这一新发现表明，ABCG1 是通过这种特定探针进行肺癌靶向治疗的潜在候选药物。此外，我们还说明了 ABCG1 与其他蛋白质的蛋白质-蛋白质相互作用（PPI）以及 ABCG1 与免疫细胞的强烈通讯。
