Метилирование гена ADCY8 в плазме крови как предиктивный маркер ответа на неоадъювантную химиотерапию рака молочной железы

Background. Neoadjuvant chemotherapy (NAC) is a common practice for locally advanced breast cancer to downstage the disease to become operable. The top-of-the-line predictor of the effectiveness of neoadjuvant treatment is the pathologic complete response, defined as the absence of viable tumor cells in the mammary gland and regional lymph nodes. According to different studies, this result is achieved in no more than 13-33% of patients. Increasing the effectiveness of NACHT can be achieved through the identification of predictive markers that allow assessing the sensitivity to therapy. Objective. To assess the methylation status of SLC9A3, DPYS, IRF4, ADCY8, KCNQ2, TERT, SYNDIG1 and SKOR2 genes in tumor and serum samples and to analyze its association with response to breast cancer neoadjuvant chemotherapy. Material and methods. Core biopsy and plasma samples were obtained before and after neoadjuvant chemotherapy from 36 primary breast cancer patients. DNA methylation status was assessed using methylation sensitive PCR. Result. DNA methylation analysis of tumor biopsy material obtained before treatment showed the following gene methylation frequencies: SLC9A3 - 27.8% (10/36), DPYS - 8.3% (3/36), IRF4 - 22.2% (8/36), ADCY8 - 41.7% (15/36), KCNQ2 - 27.8% (10/36), TERT - 8.3% (3/36), SYNDIG1 - 16.7% (6/36) and SKOR2 - 5.5% (2/36). For further investigation in the blood plasma, 3 genes with the highest methylation frequencies were selected: SLC9A3 , KCNQ2 and ADCY8 . For the ADCY8 gene in the blood plasma, a statistically significant difference in methylation frequencies (p = 0.0076, exact two-sided Fisher test) was found between groups with different degrees of therapeutic response (methylation was more often observed in the group with poor response to treatment). Conclusion. Our results indicate that the methylation status of ADCY8 gene in plasma before treatment is associated with NAC pathological complete response in breast cancer.