Abstract
BackgroundThe BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer.MethodsIn the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members’ involvement in OC by using gene set enrichment analysis.ResultsThe mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer.ConclusionIn brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.
Highlights
Ovarian cancer (OC) is a gynecological malignant tumor ranking fifth leading cause of cancer-related death in women [27]
For BolA family member 1 (BOLA1), the mRNA expression level was significantly higher in various kinds of ovarian cancer tissues than normal ovarian tissues in Lu′s dataset
Concerning BOLA2, the mRNA expressions were higher in some kinds of ovarian cancer tissues in Lu′s dataset
Summary
Ovarian cancer (OC) is a gynecological malignant tumor ranking fifth leading cause of cancer-related death in women [27]. 295,414 cases newly diagnosed, and 184,799 cases died in 2018 [3]. Most patients are diagnosed at an advanced stage due to OC’s lack of apparent symptoms in early-stage and inadequate. Previous studies showed BOLA proteins were mainly linked to stress response, iron homeostasis, and ironsulfur cluster assembly and trafficking [17]. Recent studies showed BOLA2 played critical roles in the biology and prognosis of hepatic cellular carcinoma (HCC) [12, 19]. Little knowledge about the function of the BolA gene family in other cancers. The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. There was less known about its role in ovarian cancer
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