Identification of Molecular Subtypes and a Prognostic Signature Based on Inflammation-Related Genes in Colon Adenocarcinoma

Abstract

Both tumour-infiltrating immune cells and inflammation-related genes that can mediate immune infiltration contribute to the initiation and prognosis of patients with colon cancer. In this study, we developed a method to predict the survival outcomes among colon cancer patients and direct immunotherapy and chemotherapy. We obtained patient data from The Cancer Genome Atlas (TCGA) and captured inflammation-related genes from the GeneCards database. The package "ConsensusClusterPlus" was used to generate molecular subtypes based on inflammation-related genes obtained by differential expression analysis and univariate Cox analysis. A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic factor. Cluster 2 and higher risk scores meant worse overall survival and higher expression of human leukocyte antigen and immune checkpoints. Immune cell infiltration calculated by the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumour immune dysfunction and exclusion (TIDE), and tumour stemness indices (TSIs) were also compared on the basis of inflammation-related molecular subtypes and the risk signature. In addition, analyses of stratification, somatic mutation, nomogram construction, chemotherapeutic response prediction and small-molecule drug prediction were performed based on the risk signature. We finally used qRT-PCR to detect the expression levels of four genes in colon cancer cell lines and obtained results consistent with the prediction. Our findings demonstrated a four-gene prognostic signature that could be useful for prognostication in colon cancer patients and designing personalized treatments, which could provide new versions of personalized management for these patients.

Keywords: colon adenocarcinoma; immune infiltration; inflammation; molecule subtypes; signature.