Chen Yanli, Tian Dan, Chen Xiaoqi, Tang Zhi, Li Kuina, Huang Zhijiong, Fu Yong, Feng Yanying, Yang Zhijun
Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People's Republic of China.
Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, People's Republic of China.
Int J Gen Med. 2021 Mar 22;14:967-981. doi: 10.2147/IJGM.S302012. eCollection 2021.
The dysregulation of arrestin domain containing 3 (ARRDC3) has an important effect on oncogenesis and tumor progression in many cancers, including renal cell carcinoma and breast cancer. However, the role of ARRDC3 in ovarian cancer (OC) has not been reported.
The present study explored the diagnostic and prognostic roles of ARRDC3 in ovarian cancer using GEPIA, ONCOMINE, GEO, and Kaplan-Meier Plotter databases for training and validation. Then, we conducted a stratified analysis for clinicopathological factors using Kaplan-Meier Plotter and GEPIA databases. To further explore the mechanisms, we also used the MIST database to visualize the protein-protein interaction network of ARRDC3 associated with OC. The gene-gene interaction network was visualized by GeneMANIA plugin in Cytoscape 3.8.0 software, and the associated co-expression genes of ARRDC3 were analyzed by the cBioPortal database. The 100 top co-expression genes chosen for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used by the DAVID website.
A significant difference in ARRDC3 mRNA expression was found between OC and normal ovary tissues. ARRDC3 could potentially be implicated in the diagnosis of OC. A high ARRDC3 mRNA expression level was associated with poor overall survival and progression-free survival. However, no significance was reported in respect to post progression survival. Except for histology, which had no prognostic value for PPS in stratified analysis, stratified analysis of other factors had prognostic value for OS, PFS, and PPS. Interestingly, we found a positive correlation between ARRDC3 expression and CD8+ T cells, macrophages, neutrophils, and dendritic cells, indicating that ARRDC3 might be associated with immune infiltration of these immune cells. Co-expression genes enrichment analysis found that they were involved in the Renin-angiotensin system pathway.
Differentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.
含抑制蛋白结构域3（ARRDC3）的失调在包括肾细胞癌和乳腺癌在内的多种癌症的肿瘤发生和肿瘤进展中具有重要作用。然而，ARRDC3在卵巢癌（OC）中的作用尚未见报道。
本研究利用GEPIA、ONCOMINE、GEO和Kaplan-Meier Plotter数据库进行训练和验证，探讨ARRDC3在卵巢癌中的诊断和预后作用。然后，我们使用Kaplan-Meier Plotter和GEPIA数据库对临床病理因素进行分层分析。为了进一步探究其机制，我们还使用MIST数据库来可视化与OC相关的ARRDC3的蛋白质-蛋白质相互作用网络。基因-基因相互作用网络通过Cytoscape 3.8.0软件中的GeneMANIA插件进行可视化，并且通过cBioPortal数据库分析ARRDC3的相关共表达基因。由DAVID网站使用选择的100个顶级共表达基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。
在OC组织和正常卵巢组织之间发现ARRDC3 mRNA表达存在显著差异。ARRDC3可能与OC的诊断有关。高ARRDC3 mRNA表达水平与总体生存率和无进展生存率低相关。然而，关于进展后生存率未报道有显著性差异。除组织学在分层分析中对PPS无预后价值外，其他因素的分层分析对OS、PFS和PPS均有预后价值。有趣的是，我们发现ARRDC3表达与CD8 + T细胞、巨噬细胞、中性粒细胞和树突状细胞之间呈正相关，表明ARRDC3可能与这些免疫细胞的免疫浸润有关。共表达基因富集分析发现它们参与肾素-血管紧张素系统途径。
差异表达的ARRDC3可能是卵巢癌潜在的预后和诊断标志物。
