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      ANLN functions as a key candidate gene in cervical cancer as determined by integrated bioinformatic analysis

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          Abstract

          Background

          Cervical cancer, one of the leading causes of female deaths, remains a top cause of mortality in gynecologic oncology and tends to affect younger individuals. However, the pathogenesis of cervical cancer is still far from clear. Given the high incidence and mortality of cervical cancer, uncovering the causes and pathogenesis as well as identifying novel biomarkers are of great significance and are desperately needed.

          Materials and methods

          First, raw data were downloaded from the Gene Expression Omnibus database. The Robuse Multi-Array Average algorithm and combat function of the sva package were subsequently applied to preprocess and remove batch effects. Differentially expressed genes (DEGs) analyzed with the limma package were followed by gene ontology and pathway analysis, and a protein–protein interaction (PPI) network based on the STRING website and the Cytoscape software was constructed. Weighted Correlation Network Analysis (WGCNA) was utilized to build the coexpression network. Subsequently, UALCAN websites were employed to conduct survival analysis. Finally, the oncomine database was used to validate the expression of ANLN in other datasets.

          Results

          GSE29570 and GSE89657, including 49 cervical cancer tissues and 20 normal cervical tissues, were screened as the datasets. Three-hundred-twenty-four DEGs were identified and, among them, 123 were upregulated, while 201 were downregulated. The DEGs PPI network complex, contained 305 nodes and 4,962 edges, and 8 clusters were calculated according to k-core =2. Among them, cluster 1, which had 65 nodes and 1,780 edges, had the highest score in these clusters. In coexpression analysis, there were 86 hubgenes from the Brown modules that were chosen for further analysis. Sixty-one key genes were identified as the intersecting genes of the Brown module of WGCNA and DEGs. In survival analysis, only ANLN was a prognostic factor, and the survival was significantly better in the low-expression ANLN group.

          Conclusion

          Our study suggested that ANLN may be a potential tumor oncogene and could serve as a biomarker for predicting the prognosis of cervical cancer patients.

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          Most cited references22

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          Lethality and centrality in protein networks

          In this paper we present the first mathematical analysis of the protein interaction network found in the yeast, S. cerevisiae. We show that, (a) the identified protein network display a characteristic scale-free topology that demonstrate striking similarity to the inherent organization of metabolic networks in particular, and to that of robust and error-tolerant networks in general. (b) the likelihood that deletion of an individual gene product will prove lethal for the yeast cell clearly correlates with the number of interactions the protein has, meaning that highly-connected proteins are more likely to prove essential than proteins with low number of links to other proteins. These results suggest that a scale-free architecture is a generic property of cellular networks attributable to universal self-organizing principles of robust and error-tolerant networks and that will likely to represent a generic topology for protein-protein interactions.
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            The Gene Expression Omnibus Database.

            The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome-protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/.
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              Functional Analysis of a Human Homologue of the Drosophila Actin Binding Protein Anillin Suggests a Role in Cytokinesis

              We have characterized a human homologue of anillin, a Drosophila actin binding protein. Like Drosophila anillin, the human protein localizes to the nucleus during interphase, the cortex following nuclear envelope breakdown, and the cleavage furrow during cytokinesis. Anillin also localizes to ectopic cleavage furrows generated between two spindles in fused PtK1 cells. Microinjection of antianillin antibodies slows cleavage, leading to furrow regression and the generation of multinucleate cells. GFP fusions that contain the COOH-terminal 197 amino acids of anillin, which includes a pleckstrin homology (PH) domain, form ectopic cortical foci during interphase. The septin Hcdc10 localizes to these ectopic foci, whereas myosin II and actin do not, suggesting that anillin interacts with the septins at the cortex. Robust cleavage furrow localization requires both this COOH-terminal domain and additional NH2-terminal sequences corresponding to an actin binding domain defined by in vitro cosedimentation assays. Endogenous anillin and Hcdc10 colocalize to punctate foci associated with actin cables throughout mitosis and the accumulation of both proteins at the cell equator requires filamentous actin. These results indicate that anillin is a conserved cleavage furrow component important for cytokinesis. Interactions with at least two other furrow proteins, actin and the septins, likely contribute to anillin function.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                Cancer Management and Research
                Cancer Management and Research
                Dove Medical Press
                1179-1322
                2018
                05 April 2018
                : 10
                : 663-670
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China
                [2 ]Department of Obstetrics and Gynecology, No. 455 Hospital, Shanghai, People’s Republic of China
                [3 ]Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China
                Author notes
                Correspondence: Mingjuan Xu, Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University,168 Changhai Road, Shanghai 200433, People’s Republic of China, Tel/fax +86 21 8187 0407, Email 13636373419@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                cmar-10-663
                10.2147/CMAR.S162813
                5896649
                29670400
                a6b52f4c-7a6c-4d37-847c-ce0672e07126
                © 2018 Xia et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                bioinformatics analysis,cervical cancer,wgcna,anln
                Oncology & Radiotherapy
                bioinformatics analysis, cervical cancer, wgcna, anln

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