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

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 pro...

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Autores principales: Gou, Rui, Zhu, Liancheng, Zheng, Mingjun, Guo, Qian, Hu, Yuexin, Li, Xiao, Liu, Juanjuan, Lin, Bei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717992/
https://www.ncbi.nlm.nih.gov/pubmed/31474227
http://dx.doi.org/10.1186/s12967-019-2023-z
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author Gou, Rui
Zhu, Liancheng
Zheng, Mingjun
Guo, Qian
Hu, Yuexin
Li, Xiao
Liu, Juanjuan
Lin, Bei
author_facet Gou, Rui
Zhu, Liancheng
Zheng, Mingjun
Guo, Qian
Hu, Yuexin
Li, Xiao
Liu, Juanjuan
Lin, Bei
author_sort Gou, Rui
collection PubMed
description 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.
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spelling pubmed-67179922019-09-06 Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins Gou, Rui Zhu, Liancheng Zheng, Mingjun Guo, Qian Hu, Yuexin Li, Xiao Liu, Juanjuan Lin, Bei J Transl Med Research 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. BioMed Central 2019-09-02 /pmc/articles/PMC6717992/ /pubmed/31474227 http://dx.doi.org/10.1186/s12967-019-2023-z Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Gou, Rui
Zhu, Liancheng
Zheng, Mingjun
Guo, Qian
Hu, Yuexin
Li, Xiao
Liu, Juanjuan
Lin, Bei
Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title_full Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title_fullStr Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title_full_unstemmed Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title_short Annexin A8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of Annexins
title_sort annexin a8 can serve as potential prognostic biomarker and therapeutic target for ovarian cancer: based on the comprehensive analysis of annexins
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717992/
https://www.ncbi.nlm.nih.gov/pubmed/31474227
http://dx.doi.org/10.1186/s12967-019-2023-z
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