Introduction:Ovarian cancer (OC) is the deadliest malignancy in gynecology, but the mechanism of its initiation and progression is poorly elucidated. Disulfidptosis is a novel discovered type of regulatory cell death. This study aimed to develop a novel disulfidptosis-related prognostic signature (DRPS) for OC and explore the effects and potential treatment by disulfidptosis-related risk stratification.Methods:The disulfidptosis-related genes were first analyzed in bulk RNA-Seq and a prognostic nomogram was developed and validated by LASSO algorithm and multivariate cox regression. Then we systematically assessed the clinicopathological and mutational characteristics, pathway enrichment analysis, immune cell infiltration, single-cell-level expression, and drug sensitivity according to DRPS.Results:The DRPS was established with 6 genes (MYL6, PDLIM1, ACTN4, FLNB, SLC7A11, and CD2AP) and the corresponding prognostic nomogram was constructed based on the DRPS, FIGO stage, grade, and residual disease. Stratified by the risk score derived from DRPS, patients in high-risk group tended to have worse prognosis, lower level of disulfidptosis, activated oncogenic pathways, inhibitory tumor immune microenvironment, and higher sensitivity to specific drugs including epirubicin, stauroporine, navitoclax, and tamoxifen. Single-cell transcriptomic analysis revealed the expression level of genes in the DRPS significantly varied in different cell types between tumor and normal tissues. The protein-level expression of genes in the DRPS was validated by the immunohistochemical staining analysis.Conclusion:In this study, the DRPS and corresponding prognostic nomogram for OC were developed, which was important for OC prognostic assessment, tumor microenvironment modification, drug sensitivity prediction, and exploration of potential mechanisms in tumor development.

中文翻译：

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二硫下垂相关特征阐明了卵巢癌的预后、免疫学和治疗特征

简介：卵巢癌（OC）是妇科最致命的恶性肿瘤，但其发生和进展的机制尚不清楚。二硫键死亡是一种新发现的调节性细胞死亡类型。本研究旨在为 OC 开发一种新的二硫色垂体相关预后特征 (DRPS)，并探讨二硫色垂体相关风险分层的效果和潜在治疗方法。方法：首先在批量 RNA-Seq 和预后列线图中分析二硫色垂体相关基因通过LASSO算法和多元cox回归开发和验证。然后根据DRPS系统评估其临床病理和突变特征、通路富集分析、免疫细胞浸润、单细胞水平表达和药物敏感性。结果：建立了6个基因（MYL6、PDLIM1、ACTN4、FLNB、根据 DRPS、FIGO 分期、分级和残留病构建相应的预后列线图。根据DRPS的风险评分进行分层，高危组患者预后较差，二硫化物沉积水平较低，致癌途径激活，肿瘤免疫微环境受到抑制，对表柔比星、十字孔素、纳维托克和他莫昔芬等特定药物的敏感性较高。单细胞转录组分析显示，DRPS 中基因的表达水平在肿瘤和正常组织的不同细胞类型中存在显着差异。通过免疫组化染色分析验证了DRPS中基因的蛋白水平表达。结论：本研究建立了DRPS和相应的OC预后列线图，这对于OC的预后评估、肿瘤微环境修饰、药物敏感性预测具有重要意义。 ，并探索肿瘤发展的潜在机制。