Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Biomed Res Int. 2021 Jun 2;2021:6622439. doi: 10.1155/2021/6622439. eCollection 2021.
This study was conducted to evaluate the prognostic value of receptor-interacting protein kinase 4 (RIPK4) in ovarian cancer (OC) and its role in tumorigenesis. RNA expression and the corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The relationship between clinical-pathological characteristics and RIPK4 expression was analyzed using the Wilcoxon signed-rank test and logistic regression. The Cox regression and the Kaplan-Meier method were used to evaluate the relationship between clinicopathological features and overall survival (OS). Gene set enrichment analysis (GSEA) was performed using Molecular Signatures Database. Scratch assay, transwell assay, and cell transfection were used to verify the function of RIPK4. Overexpression of RIPK4 was associated with the stage of OC and distant metastasis. Survival analysis revealed that patients with OC and higher expression of RIPK4 had a poorer prognosis. Univariate and multivariate analyses indicated that high expression of RIPK4 was associated with poor OS, as well as age and stage of OC. The areas under the curve (AUC) at 1, 4, and 8 years were 0.737, 0.634, and 0.669, respectively, according to the established OS prediction model. GSEA revealed that adherens junction, cadherin binding, and Wnt signaling pathway were enriched in the high RIPK4 expression group. Cell transfection confirmed RIPK4 was involved in the Wnt signaling pathway. RIPK4 can act as a potential prognostic molecular marker for poor survival in OC. Moreover, RIPK4 is associated with tumor metastasis and implicated in the regulation of the Wnt signaling pathway.
本研究旨在评估受体相互作用蛋白激酶 4(RIPK4)在卵巢癌(OC)中的预后价值及其在肿瘤发生中的作用。从癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库中获得 RNA 表达和相应的临床数据。使用 Wilcoxon 符号秩检验和逻辑回归分析 RIPK4 表达与临床病理特征的关系。Cox 回归和 Kaplan-Meier 方法用于评估临床病理特征与总生存期(OS)之间的关系。使用分子特征数据库进行基因集富集分析(GSEA)。划痕实验、Transwell 实验和细胞转染用于验证 RIPK4 的功能。RIPK4 的过表达与 OC 的分期和远处转移有关。生存分析表明,OC 患者中 RIPK4 表达较高的患者预后较差。单因素和多因素分析表明,RIPK4 高表达与较差的 OS 以及 OC 的年龄和分期有关。根据建立的 OS 预测模型,1、4 和 8 年的曲线下面积(AUC)分别为 0.737、0.634 和 0.669。GSEA 显示,高 RIPK4 表达组中富集了黏着连接、钙粘蛋白结合和 Wnt 信号通路。细胞转染证实 RIPK4 参与了 Wnt 信号通路。RIPK4 可以作为 OC 患者生存不良的潜在预后分子标志物。此外,RIPK4 与肿瘤转移有关,并参与调节 Wnt 信号通路。