| Objective:To investigate the potential of circulating tumor DNA(ctDNA)methylation as a predictive biomarker for neoadjuvant chemotherapy response in triple-negative breast cancer(TNBC)and construct a predictive model.Materials and Methods:The blood samples were prospectively collected from patients with TNBC who received neoadjuvant chemotherapy at the Cancer Hospital of the Chinese Academy of Medical Sciences,before and after treatment.Patients were divided into pathological complete response(pCR)and non-PCR groups based on postoperative pathological results,and clinical and pathological information was collected for both groups of patients.The ctDNA methylation sequencing data analysis was performed on patient blood samples to identify differentially methylated regions(DMRs)specific to the PCR and non-PCR groups,which were then subjected to pathway analysis.Efficacy prediction models were constructed using the PCR-specific DMRs,non-PCR-specific DMRs,and all DMRs,respectively,and their efficacy was evaluated using ROC curves.Results:A total of 14 TNBC patients were included in this study,with 6 in the PCR group and 8 in the non-PCR group.The results of univariate analysis showed that the age of patients in the PCR group was significantly younger than that in the non-PCR group(p=0.008).A total of 58 DMRs were screened by ctdna methylation sequencing analysis,including 37 PCR-specific DMRs and 21 non-PCR-specific DMRs.All DMRs showed significant differences between PCR and non-PCR patients at baseline.The distribution of DMRs in the genome is significantly different between PCR-specific and non-PCRspecific populations.KEGG pathway analysis revealed that DMR-related genes are mainly enriched in cytokine-receptor interactions,progesterone-mediated cell maturation pathway,mammalian target of rapamycin(mTOR)signaling pathway,and transcriptional regulatory signaling pathway.Based on the PCR-specific DMRs,a model was constructed,and the area under the ROC curve(AUC)was 0.875,with a sensitivity of 87.5%and specificity of 83.3%.An efficacy prediction model based on non-PCRspecific DMRs was constructed,with an ROC curve AUC of 0.896,sensitivity of 75.0%,and specificity of 100%.A model was also constructed using all DMRs,with an ROC curve AUC of 0.917,sensitivity of 75.0%,and specificity of 100%.Conclusion:The methylation status of ctDNA is correlated with the efficacy of neoadjuvant chemotherapy in TNBC patients and has potential predictive value. |
