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      Elevated CD147 expression is associated with shorter overall survival in non-small cell lung cancer

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          Abstract

          A number of studies have reported on the prognostic role of CD147 expression in non-small cell lung cancer (NSCLC); however, the results remain controversial. This study aims to investigate the impact of CD147 on the prognosis of NSCLC by means of a meta-analysis. A literature search was performed for relevant studies published before October 29, 2016. The hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated as effective measures. Sensitivity analysis and publication bias examination were also conducted. Ten eligible studies with a total of 1605 patients were included in this meta-analysis. CD147 overexpression was correlated with poor overall survival (OS) (HR=1.59, 95% CI=1.32–1.91, p<0.001). Elevated CD147 expression was associated with the presence of lymph node metastasis (OR=2.31, 95% CI=1.74–3.07, p<0.001) and advanced TNM stage (OR=3.03, 95% CI=1.24–7.39, p=0.015). However, no significant association between CD147 and sex, age, differentiation, or histology was found. No evidence of significant publication bias was identified. This meta-analysis revealed that overexpression of CD147 was associated with shorter OS, the presence of lymph node metastasis and advanced TNM stage in NSCLC. Therefore, CD147 could serve as a potential prognostic marker for NSCLC.

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          Most cited references40

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          Non-small-cell lung cancer.

          In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Trends in stage distribution for patients with non-small cell lung cancer: a National Cancer Database survey.

            We examined the recent changes in stage distribution in newly diagnosed patients with non-small cell lung cancer (NSCLC) using a national database to assess the impact of recent advances in imaging modalities. We searched the National Cancer Database for patients with NSCLC diagnosed between the calendar years 1998 and 2006 for which staging information was available. Among the 877,518 patients diagnosed with NSCLC during the study period, staging information was available for 813,302 patients (92.6%). We observed a change in stage distribution between the years 2000 and 2001, with a decrease in stage I, from 27.5 to 24.8%, and a corresponding increase in stage IV, from 35.4 to 38.8%. No significant changes in stage distribution were noted after 2002. Our study showed a recent and significant stage migration in patients with NSCLC. It is likely that increased acceptance and widespread use of (18)fluorodeoxyglucose-positron emission tomography scan and routine brain imaging could account for these changes.
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              CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression.

              CD147 is a broadly expressed plasma membrane glycoprotein containing two immunoglobulin-like domains and a single charge-containing transmembrane domain. Here we use co-immunoprecipitation and chemical cross-linking to demonstrate that CD147 specifically interacts with MCT1 and MCT4, two members of the proton-linked monocarboxylate (lactate) transporter family that play a fundamental role in metabolism, but not with MCT2. Studies with a CD2-CD147 chimera implicate the transmembrane and cytoplasmic domains of CD147 in this interaction. In heart cells, CD147 and MCT1 co-localize, concentrating at the t-tubular and intercalated disk regions. In mammalian cell lines, expression is uniform but cross-linking with anti-CD147 antibodies caused MCT1, MCT4 and CD147, but not GLUT1 or MCT2, to redistribute together into 'caps'. In MCT-transfected cells, expressed protein accumulated in a perinuclear compartment, whereas co-transfection with CD147 enabled expression of active MCT1 or MCT4, but not MCT2, in the plasma membrane. We conclude that CD147 facilitates proper expression of MCT1 and MCT4 at the cell surface, where they remain tightly bound to each other. This association may also be important in determining their activity and location.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                6 June 2017
                7 April 2017
                : 8
                : 23
                : 37673-37680
                Affiliations
                1 Nanlou Respiratory Diseases Department, Chinese PLA General Hospital, Beijing 100853, P. R. China
                Author notes
                Correspondence to: Changting Liu, changtliu@ 123456yeah.net
                Article
                16948
                10.18632/oncotarget.16948
                5514939
                28445149
                97cc8a8b-4e4b-4f8b-8814-4980578e89fb
                Copyright: © 2017 Zhang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 December 2016
                : 13 March 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                cd147,lung cancer,meta-analysis,prognosis,survival
                Oncology & Radiotherapy
                cd147, lung cancer, meta-analysis, prognosis, survival

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