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

Abstract

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.

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer

“…We utilized TISIDB ( ) to explore the relationship between the expression of genes and infiltration of tumor-infiltrating immune cells, including CD4 + T cells, CD8 + T cells, B cells, neutrophils, monocytes, eosinophils, mast cells, DCs, NKT cells, NK cells, MDSCs, and CD56 cells ( 27 , 28 ). TISIDB is an online tool that includes genomic, transcriptomic and clinical data for 30 cancer types from the TCGA database.…”

VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy

“…To further investigate the association between VISTA and cancer immunity, we utilized the Tumor and Immune System Interaction Database (TISIDB, http://cis. hku.hk/TISIDB) [44,53] to analyze the potential relevance of VISTA in multiple immune regulatory cells and molecules across 30 cancer types. In accordance with previous reports about the contradictory roles of VISTA in cancer immunity, the outcomes of integrated immunological correlation analyses showed the following: (1) VISTA expression levels correlated positively with the relative abundance of almost all types of TILs with tumor-suppressing or tumor-promoting functions across 30 types of cancers, including but not limited to, activated CD8 T cells, natural killer cells, regulatory T cells, and MDSC ( Fig.…”

Prognostic Value of ANXA8 in Gastric Carcinoma

“…Of note, ANXA8 is crucial in the maintenance of the late endosomal/lysosomal compartment physiological functions in cancer cells [16] and is able to interact with phosphatidylinositides and actin-associated membrane domains [25] which are closely related to cell migration, cytokinesis, vesicle transport and cellular immunity. It has also been clarified that high expression of ANXA8 in pancreatic cancer [20][21][22] and ovarian cancer [23] was correlated with tumor cell invasion and proliferation. ANXA8 transcription is down-regulated by EGFR and its downstream targets, phosphatidylinositol-3-kinase and Akt, are universally known as key factors of tumors proliferation, migration and metastasis [24].…”

“…Meanwhile, ANXA8 has also been linked to the formation of endosomes and epidermal growth factor receptor (EGFR) turnover in Hela cells [16]. Other reports demonstrated that the expression of ANXA8 is significantly increased in breast cancer [17][18][19], pancreatic cancer [20][21][22], ovarian cancer [23] and cholangiocarcinoma [24]. Thus, ANXA8 is expected to be a new biomarker and molecular therapeutic target for the diagnosis, treatments and prognosis of multiple diseases, especially malignant tumors.…”