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      Identification of potential diagnostic and prognostic biomarkers in non-small cell lung cancer based on microarray data

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          Abstract

          Non-small cell lung cancer (NSCLC) is the most commonly diagnosed subtype of lung cancer, and the leading cause of cancer-associated mortalities worldwide. However, NSCLC is typically diagnosed at a late stage of disease due to a lack of effective diagnostic methods. In the present study, the GSE19804 dataset was obtained from the Gene Expression Omnibus, and a number of differentially expressed genes were identified between NSCLC and adjacent normal tissues. Based on functional and pathway enrichment analyses, five hub genes (cell-division cycle 20, centromere protein F, kinesin family member 2C, BUB1 mitotic checkpoint serine/threonine kinase and ZW10 interacting kinetochore protein) were selected. After verifying that the mRNA level of these hub genes was also upregulated in NSCLC tissues by using the GSE10072 dataset and in cell lines by reverse transcription-quantitative polymerase chain reaction. The diagnostic and prognostic potentials of these five gene candidates were evaluated using receiver operating characteristic curves and survival analyses. Taken together, the present study identified five candidates that are overexpressed in NSCLC tissues and could also serve as potential diagnostic and prognostic biomarkers for patients with NSCLC.

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          Most cited references17

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          Small-cell lung cancer.

          The incidence and mortality of small-cell lung cancer worldwide make this disease a notable health-care issue. Diagnosis relies on histology, with the use of immunohistochemical studies to confirm difficult cases. Typical patients are men older than 70 years who are current or past heavy smokers and who have pulmonary and cardiovascular comorbidities. Patients often present with rapid-onset symptoms due to local intrathoracic tumour growth, extrapulmonary distant spread, paraneoplastic syndromes, or a combination of these features. Staging aims ultimately to define disease as metastatic or non-metastatic. Combination chemotherapy, generally platinum-based plus etoposide or irinotecan, is the mainstay first-line treatment for metastatic small-cell lung cancer. For non-metastatic disease, evidence supports early concurrent thoracic radiotherapy. Prophylactic cranial irradiation should be considered for patients with or without metastases whose disease does not progress after induction chemotherapy and radiotherapy. Despite high initial response rates, most patients eventually relapse. Except for topotecan, few treatment options then remain. Signalling pathways have been identified that might yield new drug targets. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Targeting Mitosis in Cancer: Emerging Strategies.

            The cell cycle is an evolutionarily conserved process necessary for mammalian cell growth and development. Because cell-cycle aberrations are a hallmark of cancer, this process has been the target of anti-cancer therapeutics for decades. However, despite numerous clinical trials, cell-cycle-targeting agents have generally failed in the clinic. This review briefly examines past cell-cycle-targeted therapeutics and outlines how experience with these agents has provided valuable insight to refine and improve anti-mitotic strategies. An overview of emerging anti-mitotic approaches with promising pre-clinical results is provided, and the concept of exploiting the genomic instability of tumor cells through therapeutic inhibition of mitotic checkpoints is discussed. We believe this strategy has a high likelihood of success given its potential to enhance therapeutic index by targeting tumor-specific vulnerabilities. This reasoning stimulated our development of novel inhibitors targeting the critical regulators of genomic stability and the mitotic checkpoint: AURKA, PLK4, and Mps1/TTK.
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              Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women.

              Although cigarette smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of smoking. The genetic mechanisms of carcinogenesis in nonsmokers are unclear, but semaphorins have been suggested to play a role as lung tumor suppressors. This report is a comprehensive analysis of the molecular signature of nonsmoking female lung cancer patients in Taiwan, with a particular focus on the semaphorin gene family. Sixty pairs of tumor and adjacent normal lung tissue specimens were analyzed by using Affymetrix U133plus2.0 expression arrays. Differentially expressed genes in tumor tissues were identified by a paired t test and validated by reverse transcriptase-PCR and immunohistochemistry. Functional analysis was conducted by using Ingenuity Pathway Analysis as well as gene set enrichment analysis and sigPathway algorithms. Kaplan-Meier survival analyses were used to evaluate the association of SEMA5A expression and clinical outcome. We identified 687 differentially expressed genes in non-small cell lung carcinoma (NSCLC). Many of these genes, most notably the semaphorin family, were participants in the axon guidance signaling pathway. The downregulation of SEMA5A in tumor tissue, both at the transcriptional and translational levels, was associated with poor survival among nonsmoking women with NSCLC. In summary, several semaphorin gene family members were identified as potential therapeutic targets, and SEMA5A may be useful as a prognostic biomarker for NSCLC, which may also be gender specific in Taiwanese patients. A novel biomarker for NSCLC is identified. ©2010 AACR.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                May 2018
                01 March 2018
                01 March 2018
                : 15
                : 5
                : 6436-6442
                Affiliations
                [1 ]Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China
                [2 ]Key Laboratory of Arrhythmias of The Ministry of Education of China, Research Institute of Heart Failure, Shanghai East Hospital, Dalian Medical University, Shanghai 200120, P.R. China
                Author notes
                Correspondence to: Dr Lei Gao, Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, P.R. China, E-mail: gldlykdx@ 123456163.com
                Article
                OL-0-0-8153
                10.3892/ol.2018.8153
                5921217
                29731852
                ef83e616-4980-44be-823c-b14025d12d04
                Copyright: © Huang 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
                : 21 December 2016
                : 01 February 2018
                Categories
                Articles

                Oncology & Radiotherapy
                bioinformatics analysis,non-small cell lung cancer,microarray data,differentially expressed genes,biomarkers

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