Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Autoimmunity. 2020 Dec;53(8):434-442. doi: 10.1080/08916934.2020.1836487. Epub 2020 Oct 20.
The GTP exchange factors on ADP-ribosylation factor (ARF) mediate the GDP/GTP exchange on ARF, serve as regulators in protein trafficking and membrane dynamics, and play critical roles in various cell processes. However, the relationship between the expression of ARF-GEF family genes and clinical implications in ovarian cancer remains unclear.
We performed a systematic investigation on the role of ARF-GEF family genes in ovarian cancer by using Gene Expression Omnibus (GEO), Kaplan-Meier plotter, Gene set enrichment analysis (GSEA), TIMER and TISIDB database.
We found that the ARF-GEF family gene CYTH4 exhibited significant expressional upregulation in ovarian cancer compared to normal ovary tissues. The expression of CYTH4 was also higher in metastases from the omentum than in matched primary ovarian tumours. Kaplan-Meier plotter showed that high expression of CYTH4 predicted worse overall survival, progression free survival and post-progression survival of ovarian cancer patients. Notably, from our correlation analysis, CYTH4 expression showed closely association with tumour-infiltrating immune cells. Intriguingly, the expression of CYTH4 was also significantly correlated with a variety of immunomodulators, chemokines and major histocompatibility complex molecules.
Overall, our findings provide a valuable source of data about the clinical significance of CYTH4 in ovarian cancer.
ADP-核糖基化因子(ARF)的 GTP 交换因子介导 ARF 的 GDP/GTP 交换,作为蛋白质运输和膜动力学的调节剂,在各种细胞过程中发挥着关键作用。然而,ARF-GEF 家族基因的表达与卵巢癌的临床意义之间的关系尚不清楚。
我们使用基因表达综合数据库(GEO)、Kaplan-Meier 绘谱器、基因集富集分析(GSEA)、TIMER 和 TISIDB 数据库,对 ARF-GEF 家族基因在卵巢癌中的作用进行了系统研究。
我们发现,与正常卵巢组织相比,ARF-GEF 家族基因 CYTH4 在卵巢癌中表现出显著的表达上调。CYTH4 的表达在大网膜转移灶中也高于匹配的原发性卵巢肿瘤。Kaplan-Meier 绘谱器显示,CYTH4 的高表达预示着卵巢癌患者的总生存期、无进展生存期和进展后生存期较差。值得注意的是,从我们的相关性分析来看,CYTH4 的表达与肿瘤浸润免疫细胞密切相关。有趣的是,CYTH4 的表达也与多种免疫调节剂、趋化因子和主要组织相容性复合物分子显著相关。
总之,我们的研究结果为 CYTH4 在卵巢癌中的临床意义提供了有价值的数据来源。