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鉴定RGS基因家族的一个具有卵巢癌预后价值的五基因特征。

Identification of a five-gene signature of the RGS gene family with prognostic value in ovarian cancer.

作者信息

Hu Yuexin, Zheng Mingjun, Wang Shuang, Gao Lingling, Gou Rui, Liu Ouxuan, Dong Hui, Li Xiao, Lin Bei

机构信息

Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, China; Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, China.

Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, China; Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, China; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.

出版信息

Genomics. 2021 Jul;113(4):2134-2144. doi: 10.1016/j.ygeno.2021.04.012. Epub 2021 Apr 9.

Abstract

The RGS (regulator of G protein signaling) gene family, which includes negative regulators of G protein-coupled receptors, comprises important drug targets for malignant tumors. It is thus of great significance to explore the value of RGS family genes for diagnostic and prognostic prediction in ovarian cancer. The RNA-seq, immunophenotype, and stem cell index data of pan-cancer, The Cancer Genome Atlas (TCGA) data, and GTEx data of ovarian cancer were downloaded from the UCSC Xena database. In the pan-cancer database, the expression level of RGS1, RGS18, RGS19, and RGS13 was positively correlated with stromal and immune cell scores. Cancer patients with high RGS18 expression were more sensitive to cyclophosphamide and nelarabine, whereas those with high RGS19 expression were more sensitive to cladribine and nelarabine. The relationship between RGS family gene expression and overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients was analyzed using the KM-plotter database, RGS17, RGS16, RGS1, and RGS8 could be used as diagnostic biomarkers of the immune subtype of ovarian cancer, and RGS10 and RGS16 could be used as biomarkers to predict the clinical stage of this disease. Further, Lasso cox analysis identified a five-gene risk score (RGS11, RGS10, RGS13, RGS4, and RGS3). Multivariate COX analysis showed that the risk score was an independent prognostic factor for patients with ovarian cancer. Immunohistochemistry and the HPA protein database confirmed that the five-gene signature is overexpressed in ovarian cancer. GSEA showed that it is mainly involved in the ECM-receptor interaction, TGF-beta signaling pathway, Wnt signaling pathway, and chemokine signaling pathway, which promote the occurrence and development of ovarian cancer. The prediction model of ovarian cancer constructed using RGS family genes is of great significance for clinical decision making and the personalized treatment of patients with ovarian cancer.

摘要

RGS(G蛋白信号调节剂)基因家族包含G蛋白偶联受体的负调控因子,是恶性肿瘤的重要药物靶点。因此,探索RGS家族基因在卵巢癌诊断和预后预测中的价值具有重要意义。从UCSC Xena数据库下载了泛癌的RNA测序、免疫表型和干细胞指数数据、癌症基因组图谱(TCGA)数据以及卵巢癌的GTEx数据。在泛癌数据库中,RGS1、RGS18、RGS19和RGS13的表达水平与基质和免疫细胞评分呈正相关。RGS18表达高的癌症患者对环磷酰胺和奈拉滨更敏感,而RGS19表达高的患者对克拉屈滨和奈拉滨更敏感。使用KM-plotter数据库分析了RGS家族基因表达与卵巢癌患者总生存期(OS)和无进展生存期(PFS)的关系,RGS17、RGS16、RGS1和RGS8可作为卵巢癌免疫亚型的诊断生物标志物,RGS10和RGS16可作为预测该疾病临床分期的生物标志物。此外,Lasso cox分析确定了一个五基因风险评分(RGS11、RGS10、RGS13、RGS4和RGS3)。多变量COX分析表明,该风险评分是卵巢癌患者的独立预后因素。免疫组织化学和HPA蛋白数据库证实,五基因特征在卵巢癌中过表达。基因集富集分析(GSEA)表明,它主要参与细胞外基质-受体相互作用、转化生长因子-β信号通路、Wnt信号通路和趋化因子信号通路,这些通路促进卵巢癌的发生和发展。利用RGS家族基因构建的卵巢癌预测模型对卵巢癌患者的临床决策和个体化治疗具有重要意义。

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