Zhang Cangang, Zhao Zhe, Liu Haibo, Yao Shukun, Zhao Dongyan
Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Northwest University, Xi'an, China.
Front Genet. 2021 Jul 12;12:657658. doi: 10.3389/fgene.2021.657658. eCollection 2021.
Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, and were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, and expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by and in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that and could function as biomarkers for prognosis and the immune response in COAD.
结肠腺癌(COAD)是最常见的恶性肿瘤之一,具有较高的迁移和侵袭能力。在本研究中,我们试图建立一个多基因特征来预测COAD患者的预后。首先应用加权基因共表达网络分析和差异基因表达分析方法,从癌症基因组图谱(TCGA)-COAD数据集和GSE39582数据集中识别COAD组织与正常组织之间差异共表达的基因,共筛选出309个重叠基因。然后,我们的研究将TCGA-COAD队列作为训练数据集,将GES39582和GSE17536数据集合并后的独立队列作为测试数据集。对这些重叠基因和训练数据集中COAD患者的总生存期(OS)进行单变量和多变量Cox回归分析后,构建了一个13基因特征,将COAD患者分为OS显著不同的高风险和低风险亚组。测试数据集使用相同的预测特征也显示出相同的结果。训练和测试数据集中预测OS的受试者工作特征分析曲线下面积分别为0.789和0.868,这表明该特征具有更强的预测能力。多变量Cox回归分析进一步表明,13基因特征可独立预测OS。在这13个预后基因中,多个COAD队列的肿瘤组织中 和 因深度缺失而下调,基于GEPIA数据库显示与较差的OS显著相关。值得注意的是, 和 的表达水平与CD8 + T细胞和树突状细胞的浸润水平呈正相关,为进一步研究 和 在COAD中的抗肿瘤免疫作用奠定了基础。综上所述,我们的研究结果表明,13基因特征可以有效地预测OS,并且 和 可以作为COAD预后和免疫反应的生物标志物。