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      Serum Insulin-Like Growth Factor Binding Protein 7 as a Potential Biomarker in the Diagnosis and Prognosis of Esophagogastric Junction Adenocarcinoma

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          Abstract

          Background/Aims

          Esophagogastric junction adenocarcinoma (EJA) is a malignant tumor associated with high morbidity and has attracted increasing attention due to a rising incidence and low survival rate. Pathological biopsy is the gold standard for diagnosis, but noninvasive and effective tests are lacking, resulting in diagnoses at advanced stages. This study explored the diagnostic value of insulin-like growth factor binding protein 7 (IGFBP7) in EJA.

          Methods

          A total of 120 EJA patients and 88 normal controls were recruited, and their serum levels of IGFBP7 were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value, and Pearson chi-square analysis was used to evaluate the correlation between IGFBP7 and clinical parameters. Kaplan-Meier survival analysis was carried out to assess the effect of IGFBP7 on overall survival (OS).

          Results

          The levels of IGFBP7 were higher in both early- and late-stage EJA patients than in normal controls (p<0.001). The area under the ROC curve for EJA patients was 0.794 (95% confidence interval [CI], 0.733 to 0.854), with a cutoff value of 2.716 ng/mL, a sensitivity of 63.3% (95% CI, 54.0% to 71.8%) and a specificity of 90.9% (95% CI, 82.4% to 95.7%). For the diagnosis of early-stage EJA, the same cutoff value and specificity were obtained, but the sensitivity of IGFBP7 was 54.3% (95% CI, 36.9% to 70.8%). Patients with low IGFBP7 protein expression had lower OS than those with high expression (p=0.034). The multivariate analysis showed that IGFBP7 is an independent prognostic factor for EJA (p=0.011).

          Conclusions

          Serum IGFBP7 acts as a potential diagnostic and prognostic marker for EJA.

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          Most cited references37

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          X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization.

          The ability to parse tumors into subsets based on biomarker expression has many clinical applications; however, there is no global way to visualize the best cut-points for creating such divisions. We have developed a graphical method, the X-tile plot that illustrates the presence of substantial tumor subpopulations and shows the robustness of the relationship between a biomarker and outcome by construction of a two dimensional projection of every possible subpopulation. We validate X-tile plots by examining the expression of several established prognostic markers (human epidermal growth factor receptor-2, estrogen receptor, p53 expression, patient age, tumor size, and node number) in cohorts of breast cancer patients and show how X-tile plots of each marker predict population subsets rooted in the known biology of their expression.
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            The insulin and insulin-like growth factor receptor family in neoplasia: an update.

            Although several early phase clinical trials raised enthusiasm for the use of insulin-like growth factor I receptor (IGF1R)-specific antibodies for cancer treatment, initial Phase III results in unselected patients have been disappointing. Further clinical studies may benefit from the use of predictive biomarkers to identify probable responders, the use of rational combination therapies and the consideration of alternative targeting strategies, such as ligand-specific antibodies and receptor-specific tyrosine kinase inhibitors. Targeting insulin and IGF signalling also needs to be considered in the broader context of the pathophysiology that relates obesity and diabetes to neoplasia, and the effects of anti-diabetic drugs, including metformin, on cancer risk and prognosis. The insulin and IGFI receptor family is also relevant to the development of PI3K-AKT pathway inhibitors.
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              Classification of adenocarcinoma of the oesophagogastric junction.

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                Author and article information

                Journal
                Gut Liver
                Gut Liver
                Gut and Liver
                Editorial Office of Gut and Liver
                1976-2283
                2005-1212
                15 November 2020
                13 December 2019
                : 14
                : 6
                : 727-734
                Affiliations
                [1 ]Department of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, Shantou, China
                [2 ]Precision Medicine Research Center, Shantou University Medical College, Shantou, China
                [3 ]Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou, China
                [4 ]Departments of Radiation Oncology, the Cancer Hospital of Shantou University Medical College, Shantou, China
                [5 ]Departments of Oncological Laboratory Research, the Cancer Hospital of Shantou University Medical College, Shantou, China
                [6 ]Department of Dermatology and Venereology, Shantou Central Hospital, Shantou, China
                [7 ]Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China
                Author notes
                Correspondence to: Yu-Hui Peng a, En-Min Li b, and Yi-Wei Xu c, aDepartment of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, Shantou 515041, China, Tel: +86-137-1591-2739, Fax: +86-754-8856-0352, E-mail: pengyuhui666@ 123456163.com , bDepartment of Biochemistry and Molecular Biology, Shantou University Medical College, No.22 Xinling Road, Shantou 515041, China, Tel: +86-138-0929-1605, Fax: +86-754-8890-0847, E-mail: nmli@ 123456stu.edu.cn , cDepartment of Clinical Laboratory Medicine, the Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, Shantou 515041, China, Tel: +86-159-8970-1200, Fax: +86-754-8856-0352, E-mail: yiwei512@ 123456126.com

                Can-Tong Liu and Yi-Wei Xu contributed equally to this work as first authors.

                Author information
                https://orcid.org/0000-0001-6479-8793
                https://orcid.org/0000-0002-8670-592X
                https://orcid.org/0000-0001-7735-2061
                https://orcid.org/0000-0002-7090-2355
                https://orcid.org/0000-0002-8107-1446
                https://orcid.org/0000-0002-7186-5242
                https://orcid.org/0000-0002-9007-0234
                https://orcid.org/0000-0002-4682-0931
                https://orcid.org/0000-0001-6375-3614
                https://orcid.org/0000-0002-1866-4679
                Article
                GNL-14-727
                10.5009/gnl19135
                7667930
                31822054
                935e36b1-13ab-4324-9b32-56b1b940ecdf
                Copyright © 2020 by The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 April 2019
                : 18 September 2019
                : 30 October 2019
                Categories
                Original Article
                Alimentary Tract

                Gastroenterology & Hepatology
                insulin-like growth factor binding protein-7,esophagogastric junction,adenocarcinoma,diagnosis,prognosis

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