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

Abstract

Introduction: Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC 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 IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival. Methods: The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC 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 of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall ­survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51–28.7, p = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group. 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 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.