Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality using 32 Genes Commonly Involved in Breast Cancer: A Retrospective Study

Abstract

Background: Invasive ductal carcinoma (IDC) breast cancer is a heterogeneous disease characterized by multiple subtypes. Breast cancer survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on breast cancer prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC breast cancer to provide further understanding of the genetic characteristics associated with poor survival. Methods: The gene mutation profiles, baseline demographics, clinicopathological variables, and treatment characteristics of the early-stage breast cancer subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 32 genes commonly involved in breast cancer were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. Results: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates were 97.6%, 96.0%, and 68.2%, respectively. The high-risk group had a significantly higher risk of poor overall survival (adjusted hazard ratio = 9.94, 95% confidence interval = 2.24–44.20, P = 0.003) than the other groups and the low-risk group did not have a significantly higher risk of poor overall survival compared with controls. Conclusions: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 10 candidate genes selected are particularly involved in cell-cycle processes, DNA repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor survival outcomes.