单位：[1]Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, China,[2]Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Northwest University, Xi’an, China,[3]Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China,[4]Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,[5]Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
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, NAT1 and NAT2 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, NAT1 and NAT2 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 NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.
基金：
National Key Development Plan for Precision Medicine Research [2017YFC0910002]
第一作者单位：[1]Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, China,
通讯作者：
通讯机构：[4]Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,[5]Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
推荐引用方式(GB/T 7714)：
Cangang Zhang,Zhe Zhao,Haibo Liu,et al.Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients[J].FRONTIERS in GENETICS.2021,12:doi:10.3389/fgene.2021.657658.
APA：
Cangang Zhang,Zhe Zhao,Haibo Liu,Shukun Yao&Dongyan Zhao.(2021).Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients.FRONTIERS in GENETICS,12,
MLA：
Cangang Zhang,et al."Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients".FRONTIERS in GENETICS 12.(2021)
