M~5C Related-regulator-mediated Methylation Modification Patterns And Prognostic Significance In Breast Cancer

Objective:Breast cancer(BC)is the most common malignancy worldwide.5-methylcytosine(m~5C)is a posttranscriptional methylation at the carbon-5 position of the cytosine base in RNA,which is closely related to the occurrence and metastasis of cancer.However,it’s mechanism in BC remains unclear.In this study,we aimed to assess the expression of m~5C regulators involved in BC and investigate their correlation with the tumor microenvironment,clinicopathological characteristics,and prognosis of BC.Methods:BC samples from TCGA and GEO databases were respectively analyzed as the training and testing sets,and identified their m~5C modification patterns based on the differential expression of m~5C-related regulators.Principal component analysis was used to construct an m~5C scoring system to individually quantify m~5C modification patterns in BC.Used Kaplan–Meier analysis and log-rank test to evaluate the value of m~5C modification in predicting prognosis.GO,KEGG,and GSEA were used to investigate the underlying pathways and functions associated with m~5C modification.ss GSEA was performed to identify m~5C modifications related to the infiltration of immune cells in the tumor microenvironment.TIDE prediction and pharmacotherapy response analysis were performed to assess the potential response to pharmacotherapy based on m~5C modification patterns.Finally,the expressions of m~5C-related regulators were measured by q RT-PCR and immunohistochemistry.Results:Three distinct m~5C modification patterns were identified in the training dataset.Based on the m~5C-related differentially expressed genes,the m~5Cscore was constructed,and divided BC patients into high and low m~5Cscore groups.Patients with a high m~5Cscore had more abundant immune cell infiltration,stronger antitumor immunity and better prognosis.However,a low m~5Cscore was linked to an enhanced response to pharmacotherapy.Finally,the potential roles of the m~5Cscore were validated in the testing dataset,and the results demonstrated the stability of the m~5Cscore and its independent prognostic value.Conclusion:This study demonstrated that the expression of m~5Cscore in breast cancer tissue was consistent with the analysis results at the molecular level through breast cancer cases,revealed the m~5Cscore is a potential tool for evaluating m~5C modification patterns,immune cell infiltration and prognosis in individual patients.This well-validated scoring model has the potential to be a novel prognostic marker for BC and has a wide range of prognostic value.