Department of Thoracic Oncology, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Sci Rep. 2024 Oct 29;14(1):25970. doi: 10.1038/s41598-024-77775-y.
Although the initial research focused on glycolysis, mitochondrial oxidative phosphorylation has become a major target of cancer cells. Cytochrome C oxidase assembly factor 6 (COA6) is a conserved assembly factor necessary for complex IV biogenesis. Nevertheless, the clinical predictive value of COA6, especially its correlation with immune cell infiltration in lung adenocarcinoma (LUAD), has not yet been elucidated. COA6 exhibited higher expression levels in LUAD cells and tumor tissues compared to normal tissues. Additionally, heightened COA6 expression was associated with reduced overall survival (OS) and advanced tumor stage. Apart from its role in mitochondrial respiratory processes, COA6 may be involved in the process of antigen binding, immunoglobulin receptor binding. Interestingly, we observed a positive correlation between COA6 expression and tumor mutational burden (TMB), as well as a significant association with decreased immune cell infiltration. COA6 was linked to resistance against gemcitabine and etoposide. We verified that COA6 was highly expressed in LUAD experimentally and cell proliferation was inhibited after COA6 knockdown. Thus, we conclude that the expression of COA6 was correlated with reduced immune cell infiltration. Additionally, COA6 functioned as a biomarker for drug sensitivity and the prognosis of lung adenocarcinoma.
虽然最初的研究集中在糖酵解上，但线粒体氧化磷酸化已成为癌细胞的主要靶点。细胞色素 C 氧化酶组装因子 6（COA6）是一种必需的保守组装因子，对于复合物 IV 的生物发生至关重要。然而，COA6 的临床预测价值，特别是其与肺腺癌（LUAD）中免疫细胞浸润的相关性，尚未阐明。COA6 在 LUAD 细胞和肿瘤组织中的表达水平明显高于正常组织。此外，COA6 表达水平升高与总生存期（OS）缩短和肿瘤分期进展相关。除了在线粒体呼吸过程中的作用外，COA6 可能参与抗原结合、免疫球蛋白受体结合的过程。有趣的是，我们观察到 COA6 表达与肿瘤突变负担（TMB）之间存在正相关，并且与免疫细胞浸润减少显著相关。COA6 与吉西他滨和依托泊苷的耐药性相关。我们验证了 COA6 在 LUAD 中高表达，并且敲低 COA6 后细胞增殖受到抑制。因此，我们得出结论，COA6 的表达与免疫细胞浸润减少相关。此外，COA6 可作为肺腺癌药物敏感性和预后的生物标志物。
