Based on Molecular Subtypes, Immune Characteristics and Genomic Variation to Constructing and Verifying Multi-Gene Prognostic Characteristics of Colorectal Cancer

Abstract

Background: Colon cancer (COAD) has been identified as being among the most prevalent tumors globally and ranked the third major contributor to cancer-related mortality. COAD is a molecularly heterogeneous disease. There are great differences in clinical manifestations and prognosis among different molecular subtypes.Methods:379 TCGA-COAD samples were divided into four subtypes: primary proliferative, with collective, crypt-like, and EMT invasion. The differences among the four subtypes were analyzed from the multidimensional perspectives of immunity, genomic variation, and prognosis. The limma package was utilized to identify differentially expressed genes (DEGs) amongst different molecular subtypes. Phenotype-related coexpressed gene modules were identified using WGCNA. The polygenic prognosis model was created utilizing the lasso Cox analysis and verified by time-dependent subject operating characteristics (ROC).Results: There are some differences in prognosis, TMB and common gene variation, immune score, and immunotherapy/chemotherapy between proliferative and three invasive molecular subtypes. 846 differential genes (DEGs) were obtained by limma packet analysis. Differential gene analysis was utilized to screen the DEGs among distinct subtypes, which were significantly enriched in the pathways related to tumorigenesis and development. Co-expression network analysis found 46 co-expressed genes correlated with proliferative and three invasive phenotypes. Based on differentially co-expressed genes, we developed a prognostic risk model of 8-genes signature, which exhibited strong stability regardless of external and internal validation. RT-PCR experiments proved the expression of eight genes in tumor and normal samples.Conclusion: We have developed an eight-gene signature prognostic stratification system. Furthermore, we proposed that this classifier can serve as a molecular diagnostic tool to assess the prognosis of colon cancer patients.