Gene signatures and cancer-immune phenotypes based on expression of WTAP and YTHDF1 in breast cancer patients

Background: N6-methyladenosine (m6A) modification, which serves as a critical regulator of transcript expression, plays an important role in regulating immune response in cancer patients. Wilms’ tumor 1-associated protein (WTAP) and YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) are respectively considered as encoder and reader in m6A regulation. The aim of this study was to investigate the relationship between WTAP and YTHDF1 gene and immunological features of breast cancer. Methods: : We investigated expression of WTAP and YTHDF1 in 1171 breast cancer samples in the Cancer Genome Atlas (TCGA) database. Patients were divided into two groups with a consensus clustering method based on WTAP and YTHDF1 expression. And then, we compared the clinical information of the patients and performed gene set enrichment analysis (GSEA) to determine the differences in functions between two groups. Immune infiltration analysis was performed using Estimate, CIBERSORT and single sample gene set enrichment analysis (ssGSEA). In addition, the expression of immune checkpoint inhibitor (ICIS) targets and tumor mutational burden were assessed in the tumor samples. Results: We determined two distinct groups of breast cancer. Group 1 had higher expression of WTAP and lower expression of YTHDF1, and group 2 expressed reversely. Group 2 had higher N stage and pathological stage compared to group 1. Group1 had stronger immune infiltration and higher expression of ICIS targets. In addition, WGCNA identified 15 genes, that were associated with WTAP and YTHDF1 expression and immune score. Conclusions: : WTAP and YTHDF1 affect the immune environment of breast cancer and may have the potential to provide new targets for immunotherapy of patients.