An Investigation on the Genetic and Epigenetic Changes of MAGE Family Genes in Breast Cancer Metastasis and Chemoresistance

Background: The investigation of genetic modifications and epigenetic controls within the melanoma antigen gene family (MAGE), the cancer-testis antigen, in breast cancer still remains elusive. The present study aimed to detect genetic and epigenetic alterations in the MAGE family genes among breast cancer patients, specifically those with metastatic breast cancer and experienced resistance to chemotherapy.Method: In this bioinformatics study, MAGE family genes were retrieved from HUGO genes database and further analyzed for protein-protein interaction using STRING version 12.0, gene ontology using DAVID v2024q2, genetic alterations using cBioPortal, receiver operating characteristic (ROC) plot using ROC plotter, prognostic value using Kaplan-Meier Plotter, DNA methylation using MethSurv, and the correlation between immune cell infiltration using TIMER 2.0. P <0.05 was considered statistically significant.Results: Patients with metastatic breast cancer have experienced genetic abnormalities in four specific genes of MAGEF1, NSMCE3, MAGEL1, and NDN. The relapse-free survival indicated that NSMCE3 and NDN have an unfavorable prognosis, while MAGEF1 and MAGEL1 have a favorable prognosis in breast cancer patients. A moderate association between the mRNA levels of MAGEF1 and MAGEL1 and the efficacy of chemotherapy was observed. The DNA methylation analysis revealed two significant CpG sites within the MAGEL1 gene in which become a poor prognosis of patients with breast cancer.Conclusion: This work has the potential to pave the way for the creation of immunotherapy and improved treatment strategy for those struggling with metastatic breast cancer and chemoresistance. Further research is guaranteed to authenticate the outcomes of these bioinformatics discoveries.