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      Diagnostic Value of Multiple Tumor Markers for Patients with Esophageal Carcinoma

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          Abstract

          Background

          Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer.

          Methods

          We systematically searched PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM), through February 28, 2013, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves.

          Results

          Of 4391 studies initially identified, 44 eligible studies including five tumor markers met the inclusion criteria for the meta-analysis, while meta-analysis could not be conducted for 12 other tumor markers. Approximately 79.55% (35/44) of the included studies were of relatively high quality (QUADAS score≥7). The summary estimates of the positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for diagnosing EC were as follows: CEA, 5.94/0.76/9.26; Cyfra21-1, 12.110.59/22.27; p53 antibody, 6.71/0.75/9.60; SCC-Ag, 7.66/0.68/12.41; and VEGF-C, 0.74/0.37/8.12. The estimated summary receiver operating characteristic curves showed that the performance of all five tumor markers was reasonable.

          Conclusions

          The current evidence suggests that CEA, Cyfra21-1, p53, SCC-Ag and VEGF-C have a potential diagnostic value for esophageal carcinoma.

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          Most cited references36

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          Hypoxia in cancer: significance and impact on clinical outcome.

          Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O(2) sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous bioreductive drugs. In many - albeit not in all - studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.
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            Global cancer statistics

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              Meta-DiSc: a software for meta-analysis of test accuracy data

              Background Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Results Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Conclusion Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at .
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 February 2015
                2015
                : 10
                : 2
                : e0116951
                Affiliations
                [1 ]Department of Preventive Medicine, Shantou University Medical College, No. 22 Xinling Road, Shantou, Guangdong, 515041, China
                [2 ]Department of International Center for Liver Disease Treatment, 302 PLA hospital, No. 100 Xisihuan Road, Beijing, 100017, China
                [3 ]Department of Medical Quality Control, 302 PLA Hospital, No. 100 Xisihuan Road, Beijing, 100017, China
                University of North Carolina School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KL. Performed the experiments: JZ ZZ YL. Analyzed the data: JZ ZX. Contributed reagents/materials/analysis tools: JZ KL XJ QY. Wrote the paper: JZ.

                Article
                PONE-D-14-37118
                10.1371/journal.pone.0116951
                4333286
                25693076
                dfd02300-d489-4b0a-839c-16b49570229d
                Copyright @ 2015

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

                History
                : 31 August 2014
                : 17 December 2014
                Page count
                Figures: 3, Tables: 2, Pages: 16
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper’s Results and Table 1.

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