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      Integrative analysis of gene expression profiles reveals distinct molecular characteristics in oral tongue squamous cell carcinoma

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          Abstract

          Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral cancer. Despite advances in knowledge regarding the genome-scale gene expression pattern of oral cancer, the molecular portrait of OTSCC biology has remained unclear over the last few decades. Furthermore, studies concerning OTSCC gene-expression profiles are limited or inconsistent owing to tissue heterogeneity in single-cohort studies. Consequently, the present study integrated the profile datasets of three cohorts in order to screen for differentially expressed genes (DEGs), and subsequently identified the potential candidate genes and pathways in OTSCC through gene enrichment analysis and protein-protein interaction (PPI) network construction. Using the selected Gene Expression Omnibus datasets GSE13601, GSE31056 and GSE78060, 206 DEGs (125 upregulated and 81 downregulated) were identified in OTSCC, principally associated with extracellular matrix (ECM) organization and the phosphoinositide 3-kinase/protein kinase B signaling pathway. Furthermore, 146/206 DEGs were filtered into the PPI network and 20 hub genes were sorted. Further results indicated that the two most significant modules filtered from the PPI network were associated with ECM organization and human papillomavirus infection, which are important factors affecting OTSCC pathology. Overall, a set of OTSCC-associated DEGs has been identified, including certain key candidate genes that may be of vital importance for diagnosis, therapy and prevention of this disease.

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.

            To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites. Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs. HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = -1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs. The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.
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              Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer

              The glycosaminoglycan hyaluronan (HA), a major component of extracellular matrices, and cell surface receptors of HA have been proposed to have pivotal roles in cell proliferation, migration, and invasion, which are necessary for inflammation and cancer progression. CD44 and receptor for HA-mediated motility (RHAMM) are the two main HA-receptors whose biological functions in human and murine inflammations and tumor cells have been investigated comprehensively. HA was initially considered to be only an inert component of connective tissues, but is now known as a “dynamic” molecule with a constant turnover in many tissues through rapid metabolism that involves HA molecules of various sizes: high molecular weight HA (HMW HA), low molecular weight HA, and oligosaccharides. The intracellular signaling pathways initiated by HA interactions with CD44 and RHAMM that lead to inflammatory and tumorigenic responses are complex. Interestingly, these molecules have dual functions in inflammations and tumorigenesis. For example, the presence of CD44 is involved in initiation of arthritis, while the absence of CD44 by genetic deletion in an arthritis mouse model increases rather than decreases disease severity. Similar dual functions of CD44 exist in initiation and progression of cancer. RHAMM overexpression is most commonly linked to cancer progression, whereas loss of RHAMM is associated with malignant peripheral nerve sheath tumor growth. HA may similarly perform dual functions. An abundance of HMW HA can promote malignant cell proliferation and development of cancer, whereas antagonists to HA-CD44 signaling inhibit tumor cell growth in vitro and in vivo by interfering with HMW HA-CD44 interaction. This review describes the roles of HA interactions with CD44 and RHAMM in inflammatory responses and tumor development/progression, and how therapeutic strategies that block these key inflammatory/tumorigenic processes may be developed in rodent and human diseases.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                February 2019
                21 December 2018
                21 December 2018
                : 17
                : 2
                : 2377-2387
                Affiliations
                [1 ]Translational Medicine Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
                [2 ]Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
                [3 ]Department of Oncoplastic and Reconstructive Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
                [4 ]Reproductive Medicine Center, Quanzhou Maternal and Child Health Hospital, Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
                [5 ]Clinical Laboratory, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
                Author notes
                Correspondence to: Dr Ying Long or Professor Yong Zeng, Translational Medicine Center, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Changsha, Hunan 410013, P.R. China, E-mail: longying@ 123456hnszlyy.com , E-mail: zengyong2011@ 123456hotmail.com
                Article
                OL-0-0-9866
                10.3892/ol.2018.9866
                6341834
                30675303
                48ba3597-f234-47d8-8791-b9dbfc9e114e
                Copyright: © Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 02 March 2018
                : 29 November 2018
                Categories
                Articles

                Oncology & Radiotherapy
                oral tongue squamous cell carcinoma,microarray,protein-protein network,integrative bioinformatics,differentially expressed gene

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