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Background  Annexins are involved in vesicle trafficking, cell proliferation and apoptosis, but their functional mechanisms in ovarian cancer remain unclear. In this study, we analyzed Annexins in ovarian cancer using different databases and selected Annexin A8 (ANXA8), which showed the greatest prognostic value, for subsequent validation in immunohistochemical (IHC) assays.    Methods  The mRNA expression levels, genetic variations, prognostic values and gene–gene interaction network of Annexins in ovarian cancer were analyzed using the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, Kaplan–Meier plotter and GeneMANIA database. ANXA8 was selected for analyzing the biological functions and pathways of its co-expressed genes, and its correlation with immune system responses via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) and the TISIDB database, respectively. We validated the expression of ANXA8 in ovarian cancer via IHC assays and analyzed its correlation with clinicopathological parameters and prognosis.    Results   ANXA2/3/8/11  mRNA expression levels were significantly upregulated in ovarian cancer, and  ANXA5/6/7  mRNA expression levels were significantly downregulated. Prognostic analysis suggested that significant correlations occurred between  ANXA2/4/8/9  mRNA upregulation and poor overall survival, and between  ANXA8/9/11  mRNA upregulation and poor progression-free survival in patients with ovarian serous tumors. Taken together, results suggested that  ANXA8  was most closely associated with ovarian cancer tumorigenesis and progression. Further analyses indicated that  ANXA8  may be involved in cell migration, cell adhesion, and vasculature development, as well as in the regulation of PI3K-Akt, focal adhesion, and proteoglycans. Additionally,  ANXA8  expression was significantly correlated with lymphocytes and immunomodulators. The IHC results showed that ANXA8 expression was higher in the malignant tumor group than in the borderline and benign tumor groups and normal ovary group, and high ANXA8 expression was an independent risk factor for survival and prognosis of ovarian cancer patients ( P  = 0.013).    Conclusions  Members of the Annexin family display varying degrees of abnormal expressions in ovarian cancer. ANXA8 was significantly highly expressed in ovarian cancer, and high ANXA8 expression was significantly correlated with poor prognosis. Therefore, ANXA8 is a high candidate as a novel biomarker and therapeutic target for ovarian cancer.

Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins