Due to high energy and material metabolism requirements, mitochondria are frequently active in tumor cells. Our study found that the high energy metabolism status is positively correlated with the poor prognosis of patients with lung adenocarcinoma. We constructed a scoring system (mitoRiskscore) based on the gene expression of specific mitochondrial localized proteins through univariate and LASSO cox regression. It has been shown that high mitoRiskscore was correlated with a shorter survival time after surgery in patients with lung adenocarcinoma. Compared with the typical TNM grading system, the mitoRiskscore gene panel had higher prediction accuracy. A vast number of external verification results ensured its universality. Additionally, the mitoRiskscore could evaluate the metabolic pattern and chemotherapy sensitivity of the tumor samples. Lung adenocarcinoma with higher mitoRiskscore was more active in glycolysis, and oxidative phosphorylation expression of proliferation-related pathway genes was also significantly upregulated. In contrast, patients with low mitoRiskscore had similar metabolic patterns to normal tissues. In order to improve the accuracy of prediction ability and promote clinical usage, we developed a nomogram that combined mitoRiskscore and clinical prognostic factors to predict the 3-year, 5-year, and 10-year survival rates of patients. We also performed in vitro experiments to verify the function of the key genes in the mitoRiskscore panel. In conclusion, the mitoRiskscore scoring system may assist clinicians to judge the postoperative survival rate and chemotherapy of patients with lung adenocarcinoma.

中文翻译：

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用于预测肺腺癌预后的基于线粒体定位蛋白的稳健面板

由于高能量和物质代谢需求，线粒体经常在肿瘤细胞中活跃。我们的研究发现，高能量代谢状态与肺腺癌患者预后不良呈正相关。我们通过单变量和 LASSO cox 回归构建了一个基于特定线粒体定位蛋白的基因表达的评分系统 (mitoRiskscore)。已经表明，高 mitoRiskscore 与肺腺癌患者术后较短的生存时间相关。与典型的 TNM 分级系统相比，mitoRiskscore 基因 panel 具有更高的预测准确度。大量的外部验证结果保证了其普遍性。此外，mitoRiskscore 可以评估肿瘤样本的代谢模式和化疗敏感性。具有较高mitoRiskscore的肺腺癌在糖酵解中更活跃，并且增殖相关途径基因的氧化磷酸化表达也显着上调。相比之下，mitoRiskscore 低的患者与正常组织具有相似的代谢模式。为了提高预测能力的准确性，促进临床应用，我们开发了一种结合mitoRiskscore和临床预后因素的列线图来预测患者的3年、5年和10年生存率。我们还进行了体外实验以验证 mitoRiskscore 面板中关键基因的功能。综上所述，mitoRiskscore评分系统可以帮助临床医生判断肺腺癌患者的术后生存率和化疗情况。