Analysis of the transcriptomic features of microsatellite instability subtype colon cancer.

ABSTRACT: BACKGROUND:Programmed cell death protein 1(PD-1) blocking antibodies have been used to enhance immunity in solid tumors and achieve durable clinical responses with an acceptable safety profile in multiple types of cancer. However, only a subset of patients could benefit from PD-1 blockade therapy. Prognostic information including PD-1 ligand (PD-L1) expression, IFN-? expression signature, tumor mutational burden, and microsatellite instability (MSI) have been evaluated for patients who are selected to receive immune checkpoint therapeutic treatment. Yet the relationship of those biomarkers in determining immune checkpoint therapy is largely unknown. METHODS:Immune-profiles of MSI subtype colon cancer were identified from integrating published MSI associated gene expression data. The enriched pathways and transcription factors were analyzed by GSEA assay. The infiltrations of immune cell types into MSI subtype colon cancer tissues were determined by CIBESORT assay. RESULTS:In the MSI subtype colon cancer patients, PD-L1, IFN-? and IFN-? associated genes are highly expressed. And all those genes are favorable effects in colon cancer progress. In addition, we find that Wnt-?-catenin and TGF? signaling pathways which are two important factors inhibiting PD-1 checkpoint blockade therapy are negatively related with MSI status. We also identify that the immune-profiles in MSI subtype colon cancer are contributed by M1 macrophage infiltration in the tumor environment. CONCLUSIONS:Our results provide the detailed underlying mechanisms of MSI subtype cancer patients are sensitive to PD-1 checkpoint blockade.

SUBMITTER: Wang H 

PROVIDER: S-EPMC6585086 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature