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      Identification of Potential Candidate Genes of Oral Cancer in Response to Chronic Infection With Porphyromonas gingivalis Using Bioinformatical Analyses

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          Abstract

          Recent investigations revealed the relationship between chronic periodontitis, Porphyromonas gingivalis and cancer. However, host genes that change in response to chronic infection with P. gingivalis and may contribute to oral cancer have remained largely unknown. In the present study, we aimed to comprehensively analyze microarray data obtained from the chronic infection model of immortalized oral epithelial cells that were persistently exposed to P. gingivalis for 15 weeks. Using protein-protein interaction (PPI) networks and Ingenuity Pathway Analysis (IPA), we identified hub genes, major biological processes, upstream regulators and genes potentially involved in tumor initiation and progression. We also validated gene expression and demonstrated genetic alteration of hub genes from clinical samples of head and neck cancer. Overall, we utilized bioinformatical methods to identify IL6, STAT1, LYN, BDNF, C3, CD274, PDCD1LG2, and CXCL10 as potential candidate genes that might facilitate the prevention and treatment of oral squamous cell carcinoma (OSCC), the most common type of head and neck squamous cell carcinoma (HNSCC).

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          Most cited references45

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

            The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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              The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation.

              The goals of this study were to better understand the ecology of oral subgingival communities in health and periodontitis and elucidate the relationship between inflammation and the subgingival microbiome. Accordingly, we used 454-pyrosequencing of 16S rRNA gene libraries and quantitative PCR to characterize the subgingival microbiome of 22 subjects with chronic periodontitis. Each subject was sampled at two sites with similar periodontal destruction but differing in the presence of bleeding, a clinical indicator of increased inflammation. Communities in periodontitis were also compared with those from 10 healthy individuals. In periodontitis, presence of bleeding was not associated with different α-diversity or with a distinct microbiome, however, bleeding sites showed higher total bacterial load. In contrast, communities in health and periodontitis largely differed, with higher diversity and biomass in periodontitis. Shifts in community structure from health to periodontitis resembled ecological succession, with emergence of newly dominant taxa in periodontitis without replacement of primary health-associated species. That is, periodontitis communities had higher proportions of Spirochetes, Synergistetes, Firmicutes and Chloroflexi, among other taxa, while the proportions of Actinobacteria, particularly Actinomyces, were higher in health. Total Actinomyces load, however, remained constant from health to periodontitis. Moreover, an association existed between biomass and community structure in periodontitis, with the proportion of specific taxa correlating with bacterial load. Our study provides a global-scale framework for the ecological events in subgingival communities that underline the development of periodontitis. The association, in periodontitis, between inflammation, community biomass and community structure and their role in disease progression warrant further investigation.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                21 February 2019
                2019
                : 9
                : 91
                Affiliations
                [1] 1Department of Periodontics, School of Stomatology, China Medical University , Shenyang, China
                [2] 2State Key Laboratory of Oral Disease, School of Stomatology, Sichuan University , Chengdu, China
                Author notes

                Edited by: Dietmar Thurnher, Medical University of Graz, Austria

                Reviewed by: Soraya Castro Trindade, State University of Feira de Santana, Brazil; Wenhui Liu, First Affiliated Hospital of Zhengzhou University, China

                *Correspondence: Yaping Pan yppan@ 123456cmu.edu.cn

                This article was submitted to Head and Neck Cancer, a section of the journal Frontiers in Oncology

                †These authors share co-first authorship

                Article
                10.3389/fonc.2019.00091
                6394248
                30847302
                326984a3-981a-46f7-a182-2412afb70955
                Copyright © 2019 Geng, Wang, Li, Liu, Zhang, Zhang and Pan.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 October 2018
                : 31 January 2019
                Page count
                Figures: 9, Tables: 0, Equations: 0, References: 62, Pages: 12, Words: 6674
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81670997
                Award ID: 81870771
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                porphyromonas gingivalis,chronic infection,inflammation,oral cancer,bioinformatics

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