Wang Xue, Lin Fei-Kai, Li Jia-Rui, Wang Hu-Sheng
Department of Obstetrics & Gynecology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, People's Republic of China.
Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Onco Targets Ther. 2020 Jun 16;13:5617-5628. doi: 10.2147/OTT.S254494. eCollection 2020.
Ovarian carcinoma is a malignant tumor with a high mortality rate and a lack of effective treatment options for patients at advanced stages. For improving outcomes and helping patients with poor prognosis, choose a suitable therapy and an excellent risk assessment model and new treatment options are needed.
Ovarian cancer gene expression profile of GSE32062 was downloaded from the NCBI GEO database for screening differentially expressed genes (DEGs) between well and poor prognosis groups using limma package in R (version 3.4.1). Prognosis-related genes and clinical prognostic factors were obtained from univariate and multivariate Cox regression analyses, and a comprehensive risk assessment model was constructed using a Pathway Dysregulation Score (PDS) matrix, Cox-Proportional Hazards (Cox-PH) regression, as well as L1-least absolute shrinkage and selection operator (L1-LASSO) penalization. Then, significant DEGs were converted to pathways and optimal prognosis-related pathways were screened. Finally, risk prediction models based on pathways, genes involved in pathways, and comprehensive clinical risk factors with pathways were built. Their prognostic functions were assessed in verification sets. Besides, genes involved in immune-pathways were checked for immune infiltration using immunohistochemistry.
A superior risk assessment model involving 9 optimal combinations of pathways and one clinical factor was constructed. The pathway-based model was found to be superior to the gene-based model. (from JAK-STAT signaling pathway) and (from DEGs) were found to be related to immune infiltration.
We have generated a comprehensive risk assessment model consisting of a clinical risk factor and pathways that showed a possible bright foreground. The set of significant pathways might play as a better prognosis model which is more accurate and applicable than the DEG set. Besides, and showing correlation to immune infiltration of ovarian cancer tissues may be potential therapeutic targets for treating ovarian cancers.
卵巢癌是一种死亡率很高的恶性肿瘤,对于晚期患者缺乏有效的治疗选择。为了改善治疗效果并帮助预后不良的患者,需要选择合适的治疗方法以及优良的风险评估模型和新的治疗方案。
从NCBI GEO数据库下载GSE32062的卵巢癌基因表达谱,使用R(版本3.4.1)中的limma软件包筛选预后良好和预后不良组之间的差异表达基因(DEG)。通过单变量和多变量Cox回归分析获得预后相关基因和临床预后因素,并使用通路失调评分(PDS)矩阵、Cox比例风险(Cox-PH)回归以及L1-最小绝对收缩和选择算子(L1-LASSO)惩罚构建综合风险评估模型。然后,将显著的DEG转换为通路并筛选出最佳的预后相关通路。最后,构建基于通路、通路中涉及的基因以及具有通路的综合临床风险因素的风险预测模型。在验证集中评估它们的预后功能。此外,使用免疫组织化学检查免疫通路中涉及的基因的免疫浸润情况。
构建了一个包含9个最佳通路组合和一个临床因素的优良风险评估模型。发现基于通路的模型优于基于基因的模型。发现(来自JAK-STAT信号通路)和(来自DEG)与免疫浸润相关。
我们生成了一个由临床风险因素和通路组成的综合风险评估模型,显示出可能的光明前景。这组显著通路可能作为一个比DEG集更准确、更适用的更好的预后模型。此外,与卵巢癌组织免疫浸润相关的和可能是治疗卵巢癌的潜在治疗靶点。