Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
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膜联蛋白 A8 可作为卵巢癌潜在的预后生物标志物和治疗靶点：基于膜联蛋白的综合分析
DOI：
10.1186/s12967-019-2023-z
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发表时间：
2019-08-20
影响因子：
7.4
通讯作者：
Lin, Bei
中科院分区：
文献类型：
--
作者：
Gou, Rui;Zhu, Liancheng;Lin, Bei
背景膜联蛋白参与囊泡运输、细胞增殖和凋亡，但其在卵巢癌中的作用机制尚不清楚。在这项研究中，我们使用不同的数据库分析了卵巢癌中的膜联蛋白，并选择了具有最大预后价值的膜联蛋白A8（ANXA 8），用于随后的免疫组化（IHC）检测中的验证。cBioPortal、Kaplan-Meier和GeneMANIA数据库。选择ANXA 8分别通过注释、可视化和集成发现数据库（大卫）和TISIDB数据库分析其共表达基因的生物学功能和途径，以及其与免疫系统反应的相关性。结果ANXA 2/3/8/11 mRNA在卵巢癌组织中表达明显上调，ANXA 5/6/7 mRNA表达明显下调。预后分析显示ANXA 2/4/8/9 mRNA表达上调与卵巢浆液性肿瘤患者总生存率低相关，ANXA 8/9/11 mRNA表达上调与卵巢浆液性肿瘤患者无进展生存率低相关。综上所述，结果表明ANXA 8与卵巢癌的发生和进展最密切相关。进一步分析表明ANXA 8可能参与细胞迁移、细胞粘附和血管发育，以及PI 3 K-Akt、粘着斑和蛋白聚糖的调节。此外，ANXA 8表达与淋巴细胞和免疫调节剂显著相关。免疫组化结果显示，ANXA 8在卵巢恶性肿瘤组中的表达高于卵巢交界性肿瘤组、良性肿瘤组和正常卵巢组，ANXA 8的高表达是影响卵巢癌患者生存和预后的独立危险因素（P= 0.013）。ANXA 8在卵巢癌组织中显著高表达，且ANXA 8高表达与预后不良显著相关。因此，ANXA 8是卵巢癌的一种新的生物标志物和治疗靶点。
BackgroundAnnexins 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.MethodsThe 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.ResultsANXA2/3/8/11mRNA expression levels were significantly upregulated in ovarian cancer, andANXA5/6/7mRNA expression levels were significantly downregulated. Prognostic analysis suggested that significant correlations occurred betweenANXA2/4/8/9mRNA upregulation and poor overall survival, and betweenANXA8/9/11mRNA upregulation and poor progression-free survival in patients with ovarian serous tumors. Taken together, results suggested thatANXA8was most closely associated with ovarian cancer tumorigenesis and progression. Further analyses indicated thatANXA8may be involved in cell migration, cell adhesion, and vasculature development, as well as in the regulation of PI3K-Akt, focal adhesion, and proteoglycans. Additionally,ANXA8expression 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).ConclusionsMembers 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.