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.
Public Health Genomics

中文翻译：

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使用乳腺癌常见基因鉴定具有高危死亡率的早期浸润性导管癌患者的候选基因：一项回顾性研究

简介：乳腺浸润性导管癌 (IDC) 是一种以多种亚型为特征的异质性疾病。IDC 存活率受到肿瘤负荷、分子亚型和基因谱的高度影响。基因突变是一种基因组不稳定性，被认为对 IDC 预后有相当大的影响。本研究使用综合生存分析，确定了候选基因和早期 IDC 患者的高风险组，以进一步了解与生存不良相关的遗传特征。方法：从开放访问数据平台下载早期 IDC 亚群的基因突变谱、基线人口统计学、临床病理变量和治疗特征。这些数据对总共 444 名患者进行了分析。共列出了 IDC 中常见的 40 个基因，并选择表现出显着差异的基因（使用对数秩检验估计）作为候选基因。结果：根据基因突变谱将患者分为对照组、低危组和高危组。低危、对照和高危患者的5年总生存率分别为97.4%、96.1%和73.0%。高危组总体生存率差的风险（调整风险比 = 6.57，95% 置信区间 = 1.51-28.7，p = 0.012）显着高于对照组，而低危组没有与对照组相比有显着的生存差异。结论：本研究提出了一种综合方法，通过典型的生存分析方法来识别候选基因，用于对这些患者的总体生存进行风险评估。选定的 14 个候选基因特别参与细胞周期过程、脱氧核糖核酸修复和耐药性；发现它们的突变通常与疾病进展或治疗抵抗有关，这通常与 IDC 的总体生存结果不佳有关。
公共卫生基因组学