线粒体功能相关基因作为结直肠癌诊断与预后标志物的应用研究

Application research of mitochondrial function-related genes as diagnostic and prognostic markers of colorectal cancer

目的 通过生物信息学的方法分析线粒体功能相关基因在结直肠癌(CRC)中的差异表达情况及其功能,并使用差异基因和临床信息构建CRC患者的诊断和预后模型,为CRC临床诊断及预后评估提供新型生物标志物。方法 基于肿瘤基因图谱数据库中CRC表达谱来筛选差异表达基因,并对差异表达线粒体相关基因进行基因本体论功能注释及京都基因和基因组百科全书功能富集。基于随机森林模型筛选与诊断相关的最优线粒体相关特征基因并绘制受试者工作特征曲线。最后采用单因素Cox回归的方法,结合临床信息分析与预后相关的线粒体相关基因,并绘制显著因素的生存曲线。结果 本研究共筛选出257个线粒体功能相关差异基因,其中包括11个线粒体基因组编码基因,它们主要与小分子分解代谢、含嘌呤化合物代谢和脂肪酸代谢等多种代谢过程有关。与诊断相关的最优线粒体相关特征基因有8个,其曲线下面积(AUC)值为0.919。单因素Cox回归分析表明,年龄≥67岁、stage分期Ⅲ&Ⅳ和MT-TL1基因表达值≥35.54是总生存时间的独立危险因素。通过风险得分绘制三年生存的AUC值为0.749,五年生存的AUC值为0.721。结论 生物信息分析结果表明线粒体功能相关基因的失调与CRC发生发展密切相关,同时建立了一种联合指标的CRC诊断及预后模型,为CRC患者的诊断及预后评估提供了新方法。

Objective To analyze the differential expression and function of mitochondrial function-related genes in colorectal cancer(CRC) through bioinformatic methods, and construct a diagnosis and prognosis model for CRC patients using the differential genes and clinical information, so as to provide new biomarkers for clinical diagnosis and prognosis evaluation of CRC. Methods Based on the CRC expression profile in The Cancer Genome Atlas database, differentially expressed genes were screened, and the differentially expressed mitochondrial-related genes were subjected to gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes function enrichment. Based on the random forest model, the optimal mitochondrial-related characteristic genes related to CRC diagnosis were identified and the receiver operating characteristic curve was drawn. Finally, the single-factor Cox regression method together with clinical information was used to analyze the mitochondrial-related genes related to CRC prognosis, and the survival curve of significant factots was plotted.Results We obtained a total of 257 mitochondrial function-related differentially expressed genes, including 11 mitochondrial-encoding genes which were mainly related to various metabolic processes such as small molecule catabolism, purine-containing compound metabolism and fatty acid metabolism. There were 8 optimal mitochondrial-related characteristic genes related to CRC diagnosis, and their area under curve(AUC) value was 0.919. Univariate Cox regression analysis showed that age≥67 years, stage Ⅲ & Ⅳ, and MT-TL1 gene expression value≥35.54 were independent risk factors for overall survival time. The AUC value for three-year survival was 0.749 and for five-year survival was 0.721. Conclusion The bioinformatics analysis shows that the dysregulation of mitochondrial function-related genes is closely related to the occurrence and development of CRC. Furthermore, a CRC diagnosis and prognosis model with combined indicators has been established, which provides a new method for the diagnosis and prognosis evaluation of CRC patients.