Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: Differentially expressed ARRDC3 might be a potential prognostic and diagnostic marker in Ovarian Cancer.
Keywords: biomarker, diagnosis, prognosis, ovarian neoplasms