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用于卵巢癌患者的 19 个 miRNA 支持向量机分类器和 6 个 miRNA 风险评分系统。

A 19‑miRNA Support Vector Machine classifier and a 6‑miRNA risk score system designed for ovarian cancer patients.

机构信息

Department of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Dongcheng, Beijing 100001, P.R. China.

出版信息

Oncol Rep. 2019 Jun;41(6):3233-3243. doi: 10.3892/or.2019.7108. Epub 2019 Apr 10.

Abstract

Ovarian cancer (OC) is the most common gynecologic malignancy with high incidence and mortality. The present study aimed to develop approaches for determining the recurrence type and identify potential miRNA markers for OC prognosis. The miRNA expression profile of OC (the training set, including 390 samples with recurrence information) was downloaded from The Cancer Genome Atlas database. The validation sets GSE25204 and GSE27290 were obtained from the Gene Expression Omnibus database. Prescreening of clinical factors was conducted using the survival package, and the differentially expressed miRNAs (DE‑miRNAs) were identified using the limma package. Using the Caret package, the optimal miRNA set was selected to build a Support Vector Machine (SVM) classifier. The miRNAs and clinical factors independently related to prognosis were analyzed using the survival package, and the risk score system was constructed. Finally, the miRNA‑target regulatory network was built by Cytoscape software, and enrichment analysis was performed. There were 46 DE‑miRNAs between the recurrent and non‑recurrent samples. After the optimal 19‑miRNA set was selected for constructing the SVM classifier, 6 DE‑miRNAs (miR‑193b, miR‑211, miR‑218, miR‑505, miR‑508 and miR‑514) independently related to prognosis were further extracted to build the risk score system. The neoplasm cancer status was independently correlated with the prognosis and conducted with stratified analysis. Additionally, the target genes in the regulatory network were enriched in the regulation of actin cytoskeleton and the TGF‑β signaling pathway. The 6‑miRNA signature may serve as a potential biomarker for OC prognosis, particularlyfor recurrence.

摘要

卵巢癌(OC)是发病率和死亡率较高的最常见妇科恶性肿瘤。本研究旨在确定 OC 的复发类型并识别潜在的 miRNA 标志物用于 OC 预后。从癌症基因组图谱数据库下载 OC 的 miRNA 表达谱(训练集,包括 390 个具有复发信息的样本)。从基因表达综合数据库获得验证集 GSE25204 和 GSE27290。使用生存包对临床因素进行预筛选,并使用 limma 包鉴定差异表达的 miRNA(DE-miRNA)。使用 Caret 包选择最佳 miRNA 集来构建支持向量机(SVM)分类器。使用生存包分析与预后独立相关的 miRNA 和临床因素,并构建风险评分系统。最后,通过 Cytoscape 软件构建 miRNA-靶标调控网络,并进行富集分析。在复发和非复发样本之间有 46 个 DE-miRNA。在选择最佳的 19-miRNA 集构建 SVM 分类器后,进一步提取 6 个与预后独立相关的 DE-miRNA(miR-193b、miR-211、miR-218、miR-505、miR-508 和 miR-514)构建风险评分系统。肿瘤癌症状态与预后独立相关,并进行分层分析。此外,调控网络中的靶基因富集在肌动蛋白细胞骨架和 TGF-β 信号通路的调控中。该 6-miRNA 特征可能成为 OC 预后的潜在生物标志物,特别是对于复发。

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