Gorbunova Anna S, Zamaraev Alexey V, Yapryntseva Maria A, Kovaleva Olga V, Tchevkina Elena M, Turkina Maria V, Zhivotovsky Boris, Kopeina Gelina S
Faculty of Medicine, MV Lomonosov Moscow State University, 119991, Moscow, Russia.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia.
Cell Death Discov. 2023 Sep 25;9(1):352. doi: 10.1038/s41420-023-01649-x.
Lung cancer is the leading cause of cancer mortality worldwide. In recent years, the incidence of lung cancer subtype lung adenocarcinoma (LUAD) has steadily increased. Mitochondria, as a pivotal site of cell bioenergetics, metabolism, cell signaling, and cell death, are often dysregulated in lung cancer cells. Mitochondria maintenance and integrity depend on mitochondrial quality control proteins (MQCPs). During lung cancer progression, the levels of MQCPs could change and promote cancer cell adaptation to the microenvironment and stresses. Here, univariate and multivariate proportional Cox regression analyses were applied to develop a signature based on the level of MQCPs (dimeric form of BNIP3, DRP1, and SIRT3) in tumorous and non-tumorous samples of 80 patients with LUAD. The MQCP signature could be used to separate the patients with LUAD into high- and low-risk groups. Survival analysis indicated that patients in the high-risk group had dramatically shorter overall survival compared with the low-risk patients. Moreover, a nomogram combining clinicopathologic features and the MQCP signature was constructed and validated to predict 1-, 3-, and 5-year overall survival of the patients. Thus, this study presents a novel signature based on MQCPs as a reliable prognostic tool to predict overall survival for patients with LUAD.
肺癌是全球癌症死亡的主要原因。近年来,肺癌亚型肺腺癌(LUAD)的发病率稳步上升。线粒体作为细胞生物能量学、新陈代谢、细胞信号传导和细胞死亡的关键场所,在肺癌细胞中常常失调。线粒体的维持和完整性依赖于线粒体质量控制蛋白(MQCPs)。在肺癌进展过程中,MQCPs的水平可能会发生变化,并促进癌细胞适应微环境和应激。在此,应用单变量和多变量比例Cox回归分析,基于80例LUAD患者肿瘤和非肿瘤样本中MQCPs(BNIP3二聚体形式、DRP1和SIRT3)的水平开发了一种特征。该MQCP特征可用于将LUAD患者分为高风险组和低风险组。生存分析表明,高风险组患者的总生存期明显短于低风险患者。此外,构建并验证了一个结合临床病理特征和MQCP特征的列线图,以预测患者1年、3年和5年的总生存期。因此,本研究提出了一种基于MQCPs的新型特征,作为预测LUAD患者总生存期的可靠预后工具。