Li Xiao-Xue, Xiong Li, Wen Yu, Zhang Zi-Jian
Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Genet. 2021 Nov 15;12:774400. doi: 10.3389/fgene.2021.774400. eCollection 2021.
The early diagnosis of ovarian cancer (OC) is critical to improve the prognosis and prevent recurrence of patients. Nevertheless, there is still a lack of factors which can accurately predict it. In this study, we focused on the interaction of immune infiltration and ferroptosis and selected the ESTIMATE algorithm and 15 ferroptosis-related genes (FRGs) to construct a novel E-FRG scoring model for predicting overall survival of OC patients. The gene expression and corresponding clinical characteristics were obtained from the TCGA dataset (n = 375), GSE18520 (n = 53), and GSE32062 (n = 260). A total of 15 FRGs derived from FerrDb with the immune score and stromal score were identified in the prognostic model by using least absolute shrinkage and selection operator (LASSO)-penalized COX regression analysis. The Kaplan-Meier survival analysis and time-dependent ROC curves performed a powerful prognostic ability of the E-FRG model via multi-validation. Gene Set Enrichment Analysis and Gene Set Variation Analysis elucidate multiple potential pathways between the high and low E-FRG score group. Finally, the proteins of different genes in the model were verified in drug-resistant and non-drug-resistant tumor tissues. The results of this research provide new prospects in the role of immune infiltration and ferroptosis as a helpful tool to predict the outcome of OC patients.
卵巢癌（OC）的早期诊断对于改善患者预后和预防复发至关重要。然而，仍然缺乏能够准确预测它的因素。在本研究中，我们聚焦于免疫浸润与铁死亡的相互作用，选择ESTIMATE算法和15个铁死亡相关基因（FRGs）构建了一种新型的E-FRG评分模型，用于预测OC患者的总生存期。基因表达及相应临床特征数据来自TCGA数据集（n = 375）、GSE18520（n = 53）和GSE32062（n = 260）。通过使用最小绝对收缩和选择算子（LASSO）惩罚的COX回归分析，在预后模型中确定了总共15个来自FerrDb并带有免疫评分和基质评分的FRGs。Kaplan-Meier生存分析和时间依赖性ROC曲线通过多次验证显示了E-FRG模型强大的预后能力。基因集富集分析和基因集变异分析阐明了高E-FRG评分组和低E-FRG评分组之间的多个潜在通路。最后，在耐药和非耐药肿瘤组织中验证了模型中不同基因的蛋白质。本研究结果为免疫浸润和铁死亡在预测OC患者预后方面的作用提供了新的前景。
