Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Immunol. 2022 Sep 13;13:959967. doi: 10.3389/fimmu.2022.959967. eCollection 2022.
The prognosis for colon adenocarcinoma (COAD) today remains poor. Changes in mitochondria-related genes and metabolic reprogramming are related to tumor growth, metastasis, and immune evasion and are key factors in tumor genesis and development.
TCGA database was used to analyze the differentially expressed mitochondrial energy metabolism pathway-related genes (MMRGs) in COAD patients, and the mutation of MMRG in tumor cells, the biological processes involved, and the correlation with tumor immunity were also analyzed. Then, MMRG and MMRG-related genes were used to divide COAD patients into different subtypes, and immunocorrelation analysis and survival analysis were performed. Finally, univariate regression analysis and LASSO regression analysis were used to construct a prognostic risk model for COAD patients, which was verified by the GEO database and evaluated by Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves, and the correlation between the risk model and immunity and clinical subtypes based on MMRG was analyzed.
In this study, the MMRG patterns and tumor immune microenvironment characteristics in COAD patients were systematically evaluated by clustering the expression of 188 MMRGs. We identified two subtypes of COAD with different clinical and immunological characteristics. Eight of the 28 differentially expressed MMRG genes were used to construct risk scores. ROC and K-M curves suggested that the risk model could well predict the prognosis of COAD patients, and the risk model was related to immune cell infiltration and immune function.
The two COAD subtypes identified by MMRG are helpful for the clinical differentiation of patients with different prognoses and tumor progressions, and the risk score can assist the clinical evaluation of patient prognosis. Our results suggest that CPT2 contributes to the recruitment and regulation of neutrophils in COAD. CPT2 may act as a valuable biomarker for COAD immunotherapy.
目前，结肠癌（COAD）的预后仍然较差。与肿瘤生长、转移和免疫逃逸相关的线粒体相关基因和代谢重编程的变化是肿瘤发生和发展的关键因素。
使用 TCGA 数据库分析 COAD 患者中差异表达的线粒体能量代谢途径相关基因（MMRGs），分析肿瘤细胞中 MMRG 的突变、涉及的生物学过程以及与肿瘤免疫的相关性。然后，使用 MMRG 和 MMRG 相关基因将 COAD 患者分为不同的亚型，并进行免疫相关性分析和生存分析。最后，使用单变量回归分析和 LASSO 回归分析构建 COAD 患者的预后风险模型，通过 GEO 数据库进行验证，并通过 Kaplan-Meier（K-M）和接收者操作特征（ROC）曲线进行评估，并分析基于 MMRG 的风险模型与免疫和临床亚型的相关性。
本研究通过对 188 个 MMRG 表达进行聚类，系统评估了 COAD 患者的 MMRG 模式和肿瘤免疫微环境特征。我们鉴定了两种具有不同临床和免疫学特征的 COAD 亚型。使用 28 个差异表达的 MMRG 基因中的 8 个构建风险评分。ROC 和 K-M 曲线表明，风险模型可以很好地预测 COAD 患者的预后，并且风险模型与免疫细胞浸润和免疫功能有关。
通过 MMRG 鉴定的两种 COAD 亚型有助于不同预后和肿瘤进展患者的临床区分，风险评分可辅助临床评估患者的预后。我们的结果表明 CPT2 有助于 COAD 中中性粒细胞的募集和调节。CPT2 可能是 COAD 免疫治疗的有价值的生物标志物。
