Background/Objectives:This study aimed to construct a risk score (RS) based on necroptosis-associated genes to predict the prognosis of patients with advanced epithelial ovarian cancer (EOC).Methods:EOC data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) series 140082 (GSE140082) were used. Based on known necroptosis-associated genes, clustering was performed to identify molecular subtypes of EOC. A least absolute shrinkage and selection operator (LASSO)–Cox regression analysis identified key genes related to prognosis. The expression of one of them,RIPK3, was analyzed via immunohistochemistry in an EOC cohort.Results:An RS made from ten genes (IDH2,RIPK3,FASLG,BRAF,ITPK1,TNFSF10,ID1,PLK1,MLKLandHSPA4) was developed. Tumor samples were divided into a high-risk group (HRG) and low-risk group (LRG) using the RS. The model is able to predict the overall survival (OS) of EOC and distinguish the prognosis of different clinical subgroups. Immunohistochemical verification of the receptor-interacting serine/threonine-protein kinase (RIPK) 3 confirmed that high nuclear expression is correlated with a longer OS. In addition, the score can predict the response to a programmed death ligand 1 (PD-L1) blockade treatment in selected solid malignancies. Patients from the LRG seem to benefit more from it than patients from the HRG.Conclusions:Our RS based on necroptosis-associated genes might help to predict the prognosis of patients with advanced EOC and gives an idea on how the use of immunotherapy can potentially be guided.
背景/目的：本研究旨在构建基于坏死性凋亡相关基因的风险评分，以预测晚期上皮性卵巢癌患者的预后。方法：利用癌症基因组图谱数据库及基因表达综合数据库GSE140082系列中的上皮性卵巢癌数据。基于已知的坏死性凋亡相关基因进行聚类分析，识别上皮性卵巢癌的分子亚型。通过最小绝对收缩与选择算子-Cox回归分析确定与预后相关的关键基因，并采用免疫组化方法在上皮性卵巢癌队列中验证其中RIPK3基因的表达情况。结果：构建了由十个基因（IDH2、RIPK3、FASLG、BRAF、ITPK1、TNFSF10、ID1、PLK1、MLKL和HSPA4）组成的风险评分模型。根据风险评分将肿瘤样本分为高风险组和低风险组。该模型能有效预测上皮性卵巢癌患者的总生存期，并区分不同临床亚组的预后差异。受体相互作用丝氨酸/苏氨酸蛋白激酶3的免疫组化验证证实，其细胞核高表达与较长总生存期相关。此外，该评分模型可预测特定实体恶性肿瘤对程序性死亡配体1阻断治疗的反应，低风险组患者较高风险组患者可能获得更大临床获益。结论：基于坏死性凋亡相关基因构建的风险评分模型有助于预测晚期上皮性卵巢癌患者的预后，并为免疫治疗的临床应用提供潜在指导。
Necroptosis-Related Gene Signature Predicts Prognosis in Patients with Advanced Ovarian Cancer
肿瘤(癌症)患者之家