肺腺癌（LUAD）是最普遍的肺癌之一，也是导致死亡的主要原因之一。以往的研究发现肺腺癌与戊二醛脱氢酶2（ALDH2）存在联系，后者是醛脱氢酶基因超家族的一员。本研究通过分析LUAD患者ALDH2的表达水平、表观遗传机制和信号活动等，识别出了额外的用于早期LUAD识别和瞄准LUAD治疗的有用预测标志物。研究结果表明，ALDH2基因和蛋白表达在LUAD患者样本中显著下调。此外，美国癌症联合委员会（AJCC）报告认为，ALDH2表达降低与不同阶段的LUAD患者综合生存率密切相关。值得注意的是，ALDH2在LUAD癌症中存在异常的DNA甲基化状态。在多个细胞生物信号通路的蛋白组表达谱中，ALDH2被发现在干细胞相关的通路中下调。最后，报告了ALDH2活性与干细胞相关因子和免疫系统之间的关系。总之，ALDH2下调、DNA甲基化异常和干细胞信号通路缺失是LUAD相关的预测和治疗标志物。© 2023 The Author(s)。

Lung adenocarcinoma (LUAD) is the most prevalent lung cancer and one of the leading causes of death. Previous research found a link between LUAD and Aldehyde Dehydrogenase 2 (ALDH2), a member of aldehyde dehydrogenase gene (ALDH) superfamily. In this study, we identified additional useful prognostic markers for early LUAD identification and targeting LUAD therapy by analyzing the expression level, epigenetic mechanism, and signaling activities of ALDH2 in LUAD patients. The obtained results demonstrated that ALDH2 gene and protein expression significantly downregulated in LUAD patient samples. Furthermore, The American Joint Committee on Cancer (AJCC) reported that diminished ALDH2 expression was closely linked to worse overall survival (OS) in different stages of LUAD. Considerably, ALDH2 showed aberrant DNA methylation status in LUAD cancer. ALDH2 was found to be downregulated in the proteomic expression profile of several cell biology signaling pathways, particularly stem cell-related pathways. Finally, the relationship of ALDH2 activity with stem cell-related factors and immune system were reported. In conclusion, the downregulation of ALDH2, abnormal DNA methylation, and the consequent deficit of stemness signaling pathways are relevant prognostic and therapeutic markers in LUAD.© 2023 The Author(s).