Identification and Prognostic Value Exploration of Cyclophosphamide (Cytoxan)-Centered Chemotherapy Response-Associated Genes in Breast Cancer

In this study, we aimed to explore cyclophosphamide (Cytoxan) response-associated genes and constructed a model to predict the prognosis of breast cancer (BRCA) patients. Samples obtained from TCGA and GEO databases were subjected to Weighted Gene Coexpression Network Analysis (WGCNA) and univariate Cox and LASSO Cox regression analysis to identify and validate the Cytoxan response-related prognostic signature. Moreover, multivariate Cox regression analysis was performed to analyze the independence of factors, and the nomogram model was constructed by including all the independent factors. WGCNA revealed that 159 genes are significantly correlated with Cytoxan response in BRCA samples, and the samples with a different prognosis could be effectively distinguished based on the expression of those 159 genes. Ten genes were further selected to be related to the prognosis of BRCA patients, including PCDHB2, GRIK2, FRMD7, CCSER1, PCDHGA1, PCDHA1, LRRC37A6P, PCDHGA12, ZNF486, and PCDHGB5, based on the Risk Score model. Among them, PCDHA1 expression was validated in cells and patient samples. Multivariate Cox regression analysis confirmed that the Risk Score is an independent factor. Furthermore, the nomogram model showed that the predicted survival probability is closely related to the actual survival probability. In conclusion, we identified 159 genes potentially correlated with the Cytoxan response of BRCA patients, which had prognostic value in BRCA.