上皮性卵巢癌（EOC）的总体生存率较低，这主要是由于频繁复发和对铂类化疗产生耐药性。具有同源重组 (HR) 缺陷的 EOC 对铂类化疗的敏感性增加，因为铂类诱导的 DNA 损伤无法修复。 HR 通路中涉及的基因突变被认为与治疗的良好反应密切相关。携带这些突变的患者有更好的预后和更高的生存率。另一方面，EOC 中非 HR 基因的突变与化疗耐药性增加和预后较差相关。因此，准确预测治疗反应和总体生存率仍然具有挑战性。因此，NCI 癌症基因组图谱 (TCGA) 计划对 360 个 EOC 病例进行了分析，以确定与总体生存率密切相关的新基因突变特征。我们发现相当一部分 EOC 病例在一组 31 个基因中表现出多重且重叠的突变。使用对来自 TCGA 的突变谱和患者生存数据的逻辑回归模型，我们确定了 EOC 患者中特定的有害基因突变组是否对患者生存有影响。我们的结果显示，与生存时间延长密切相关的六个基因是 BRCA1、NBN、BRIP1、RAD50、PTEN 和 PMS2。此外，我们的分析显示与生存时间缩短密切相关的 6 个基因是 FANCE、FOXM1、KRAS、FANCD2、TTN 和 CSMD3。此外，根据这些阳性和阴性基因突变特征对 360 名患者进行 Kaplan-Meier 生存分析，证实了我们的回归模型优于传统的基于 HR 基因的生存结果分类和预测。总的来说，我们的研究结果表明，EOC 表现出 HR 基因突变之外的独特突变特征。我们的方法可以识别一组新的基因突变，有助于改善对 EOC 患者的治疗结果和总体生存率的预测。版权所有：© 2024 Ma 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment. Patients with these mutations have better prognosis and an improved survival rate. On the other hand, mutations in non-HR genes in EOC are associated with increased chemoresistance and poorer prognosis. For this reason, accurate predictions in response to treatment and overall survival remain challenging. Thus, analyses of 360 EOC cases on NCI's The Cancer Genome Atlas (TCGA) program were conducted to identify novel gene mutation signatures that were strongly correlated with overall survival. We found that a considerable portion of EOC cases exhibited multiple and overlapping mutations in a panel of 31 genes. Using logistical regression modeling on mutational profiles and patient survival data from TCGA, we determined whether specific sets of deleterious gene mutations in EOC patients had impacts on patient survival. Our results showed that six genes that were strongly correlated with an increased survival time are BRCA1, NBN, BRIP1, RAD50, PTEN, and PMS2. In addition, our analysis shows that six genes that were strongly correlated with a decreased survival time are FANCE, FOXM1, KRAS, FANCD2, TTN, and CSMD3. Furthermore, Kaplan-Meier survival analysis of 360 patients stratified by these positive and negative gene mutation signatures corroborated that our regression model outperformed the conventional HR genes-based classification and prediction of survival outcomes. Collectively, our findings suggest that EOC exhibits unique mutation signatures beyond HR gene mutations. Our approach can identify a novel panel of gene mutations that helps improve the prediction of treatment outcomes and overall survival for EOC patients.Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.