| Background and Purpose:N6-methyladenosine(m6A)is an important regulator of epigenetic modification that governs tumor self-renewal and cell fate.WTAP and YTHDF1 serve as the encoder and reader,respectively,in the m6 A modification process.Recently,immunotherapy has exhibited promising therapeutic efficacy in breast tumors,and the immune environment has garnered increasing attention in the progression and treatment of cancer.The objective of this study is to investigate the correlation between the WTAP/YTHDF1 genes and the immunological features of breast cancer(BRCA).Methods:We studied the expression levels of WTAP and YTHDF1 in 1171 breast tissue samples from The Cancer Genome Atlas(TCGA)database.Patients were divided into two groups based on a consistent clustering method of WTAP and YTHDF1 expression levels.Clinical information of patients was compared between the two groups and gene set enrichment analysis(GSEA)was conducted to identify functional differences between the two groups.Immune infiltration analysis was performed using ESTIMATE,CIBERSORT,and single-sample gene set enrichment analysis(ss GSEA).Additionally,we evaluated the expression of immune checkpoint inhibitors(ICIS)targets and tumor mutational burden(TMB)in the tumor samples.The immunological features between the two groups were externally validated using GSE20685,and RT-q PCR was performed in vitro to confirm the expression differences of WTAP and YTHDF1 in breast cancer and adjacent tissues.GSE20685 was used to externally validate the immunological features between the two groups,and RT-q PCR was performed in vitro to confirm the expression differences of WTAP and YTHDF1 in breast cancer and adjacent tissues.Results:We divided breast cancer patients into two groups based on the expression levels of WTAP and YTHDF1 using consistency clustering analysis.Group 1 had a high expression of WTAP and a low expression of YTHDF1,while group 2 had low WTAP expression and high YTHDF1 expression.The lymph node staging in group 2was significantly higher than that in group 1.Immune infiltration analysis showed that immune cell infiltration and the expression of immune checkpoints and tumor mutational burden were higher in group 1.In addition,WGCNA identified 15 genes that were associated with the expression of WTAP and YTHDF1 and immune scores.Conclusion:The expression of WTAP and YTHDF1 may be associated with the immune infiltration of breast cancer and could provide new targets for breast cancer immunotherapy.Patients in Group 1(high expression of WTAP and low expression of YTHDF1)showed significantly higher levels of immune cell infiltration,immune checkpoint expression,and tumor mutational burden than those in Group 2(low expression of WTAP and high expression of YTHDF1).These results suggest that Group 1 patients have stronger anti-tumor immunity and may have a better response to immunotherapy. |
