Exploration of the role of tumor mutation burden in clinical significance, immunotherapy response predictor and immune cell infiltration in colon cancer

Abstract

Backgroud:Tumor mutation burden has become a powerful bio-marker to predict prognosis and immunotherapy responsiveness to patients in various cancers, but the role of TMB in colon cancer is still unclear.Methods:The transcriptome profiling data of colon patients and the simple nucleotide variation data of colon cases were downloaded from the Cancer Genome Atlas (TCGA) database. The groups were divided into high TMB and low TMB group according to the median of TMB. Then we explored the relationship between immune checkpoints, immune cells and TMB, respectively. Results: Mutation profiles of 399 colon cancer samples were analyzed in TCGA database. The senior (age＞65) had a strong relationship with higher-TMB level(p=0.001). Low-TMB group correlated with advanced N stage (P＜0.001), M stage (P＜0.001), and pathologic stage(P＜0.001). High-TMB group had significantly higher mRNA level of PD-L1, TIGIT, HAVCR2, and LAG3 than low-TMB group, which indicated high-TMB referred to better immunotherapy responsiveness in colon cancer. And high-TMB level correlated with higher fractions of CD8T cells (p=0.021), higher CD4 memory T cells(p=0.039), follicular helper T cells (p=0.002)and M1 macrophages (p＜0.001), while the low-TMB groups correlated with higher regulator T cells (p=0.002). So high-TMB correlated with stronger immune cell infiltrationConclusions:The high TMB referred to better clinical pathologic features, better immunotherapy responsiveness and stronger immune cells infiltration in colon cancer. Hence TMB may be a very promising bio-marker to predict prognosis and immunotherapy responsiveness to patients in colon cancer.