Fashion and Appropriation

PURPOSE: Drug resistance is a major cause of treatment failure in breast cancer patients. Numerous genetic and epigenetic markers have been proposed to influence Neoadjuvant Chemotherapy (NACT) response, and genes that regulate the effectiveness of chemotherapeutic agents undergo expression regulation via methylation. In this study, we aimed to investigate the methylation levels of KDM5A, KDM5B, and KDM5C, as well as their associated genes, EZH2, TFAP2C, ZMYND8, and SIN3B (Exon 1-2 and 19-20), in blood samples collected from patients before and after NACT treatment. Besides, we also examined potential variations in the KDM5A, KDM5B, and KDM5C gene regions. METHODS: Twenty patients were diagnosed with breast cancer, and 30 healthy control individuals were included in the study. Blood samples were taken from the patients twice, before and after NACT. Methylation levels of KDM5 family genes and related genes were analyzed using Methylation-specific PCR (MSP). Additionally, potential variants in the KDM5A, KDM5B, and KDM5C gene regions were identified using Sanger sequencing. RESULTS: According to the methylation analysis results, the SIN3B (Exon 19-20), KDM5C, EZH2, and TFAP2C genes were prominent in patients with pathological partial response, while the KDM5A, KDM5B, KDM5C, EZH2, TFAP2C, and SIN3B (Exon 19-20) genes were prominent in patients with pathological complete response. According to genotyping results, rs41308616 and rs971896841 variants were detected as heterozygous in the KDM5C gene region in two patients, respectively. CONCLUSION: The methylation percentages and genetic variations in the KDM5 family and related gene regions identified in this study may serve as potential biomarkers for developing treatment strategies for breast cancer patients.