Cong Yunyan, Cai Guangyao, Ding Chengcheng, Zhang Han, Chen Jieping, Luo Shiwei, Liu Jihong
Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Front Genet. 2024 Apr 17;15:1378907. doi: 10.3389/fgene.2024.1378907. eCollection 2024.
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.
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.
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.
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.
卵巢癌（OC）是妇科最致命的恶性肿瘤，但其发生和发展机制尚不清楚。二硫化物诱导的细胞死亡是一种新发现的调节性细胞死亡类型。本研究旨在开发一种新的OC二硫化物诱导的细胞死亡相关预后特征（DRPS），并通过二硫化物诱导的细胞死亡相关风险分层探讨其作用及潜在治疗方法。
首先在批量RNA测序中分析二硫化物诱导的细胞死亡相关基因，并通过LASSO算法和多变量cox回归开发和验证预后列线图。然后，我们根据DRPS系统评估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。
由6个基因（MYL6、PDLIM1、ACTN4、FLNB、SLC7A11和CD2AP）建立了DRPS，并基于DRPS、国际妇产科联盟（FIGO）分期、分级和残留疾病构建了相应的预后列线图。根据DRPS得出的风险评分进行分层，高危组患者预后往往较差，二硫化物诱导的细胞死亡水平较低，致癌通路激活，肿瘤免疫微环境受到抑制，对表柔比星、斯托罗泊宁、维托司他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，肿瘤组织和正常组织之间不同细胞类型中DRPS基因的表达水平存在显著差异。通过免疫组织化学染色分析验证了DRPS基因的蛋白水平表达。
本研究开发了OC的DRPS和相应的预后列线图，这对于OC预后评估、肿瘤微环境修饰、药物敏感性预测以及肿瘤发生潜在机制的探索具有重要意义。
