Identification of a novel gene signature with DDR and EMT difunctionalities for predicting prognosis, immune activity, and drug response in breast cancer

Abstract

Abstract Breast cancer (BRCA) is one of the leading causes of female death worldwide. There are substantial evidences that DNA damage repair (DDR) and epithelial-mesenchymal transition (EMT) are critically related to cancer’s progression and treatment. Nevertheless, it has not been illuminated whether genes with the two functions play a more crucial role in the prognosis, immune and therapy response of BRCA patients. In this study, We identified the prognostic-related genes with both DDR and EMT functions and explored the immune infiltration and chemosensitivity between the different risk groups. The transcriptome expression data and clinical information of BRCA patients were extracted from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The univariate Cox regression analysis was used to screen the prognosis-related DEDGs. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed to construct a prognosis model. Additionally, the multivariate COX regression was conducted to construct a prognostic nomogram. ESTIMATE algorithm, ssGSEA, and the IC50 of chemotherapeutic drugs were used to assess immune activity and responsiveness to chemotherapy. And the prognostic model of six DEDGs were validated in two independent GEO cohorts. The study found that the high-risk group’s patients had significantly lower survival rates than the low-risk group. The immune infiltration levels were lower in the high-risk group. Moreover, patients in the high-risk group were more insensitive to chemotherapeutic agents. This study provides a theoretical framework for BRCA’s treatment and contributing into individualized therapy strategies in BRCA.