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      The clinicopathological significance of CDH1 in gastric cancer: a meta-analysis and systematic review


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          CDH1 is a protein encoded by the CDH1 gene in humans. Loss of CDH1 function contributes to cancer progression by increasing proliferation, invasion, and/or metastasis. However, the association and clinicopathological significance between CDH1 hypermethylation and gastric cancer (GC) remains unclear. In this study, we systematically reviewed the studies of CDH1 hypermethylation and GC, and evaluated the association between CDH1 hypermethylation and GC using meta-analysis methods.


          A comprehensive search of the PubMed and Embase databases was performed for publications up to July 2014. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized.


          A final analysis of 1,079 GC patients from 14 eligible studies was performed. CDH1 hypermethylation level in the cancer group was significantly higher compared to the normal gastric mucosa (OR =8.55, 95% confidence interval [CI]: 2.39–33.51, Z=5.47, P<0.00001). CDH1 hypermethylation was not significantly higher in GC than in adjacent gastric mucosa (OR =3.68, 95% CI: 0.96–14.18, Z=1.90, P=0.06). However, CDH1 hypermethylation was higher in adjacent gastric mucosa compared to that in normal gastric mucosa (OR =2.55, 95% CI: 1.22–5.32, Z=2.49, P<0.01). In addition, CDH1 hypermethylation was correlated with Helicobacter pylori (HP) status in GC. The pooled OR from six studies including 280 HP-positive GCs and 193 HP-negative GCs is 1.72 (95% CI: 1.13–2.61, Z=2.55, P=0.01).


          The results of this meta-analysis reveal that CDH1 hypermethylation levels in cancer and adjacent gastric mucosa are significantly higher compared to normal gastric mucosa. Thus, CDH1 hypermethylation is significantly correlated with GC risk. CDH1 hypermethylation is correlated with HP status, indicating that it plays a more important role in the pathogenesis of HP-positive GC and might be an interesting potential drug target for GC patients.

          Most cited references39

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          Cadherins: a molecular family important in selective cell-cell adhesion.

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            Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.

            E-cadherin (E-cad) is a subclass of the cadherin family that plays a major role in maintenance of intercellular junctions in epithelial tissues. In order to explore the correlation between the expression of E-cad and cancer invasion and metastasis in vivo, we performed an immunohistochemical examination for E-cad expression in 120 patients with breast cancer using our specific anti-E-cad monoclonal antibody. In noncancerous epithelial cells, E-cad was strongly expressed on cell-cell boundaries, whereas various staining patterns were observed in tumors. Of these 120 tumors, 56 (47%) showed Pr type expression of E-cad, and 64 (53%) showed Rd type or negative expression. We found significant correlations between E-cad expression and clinicopathological features. The frequency of Rd type was significantly higher in invasive ductal carcinomas (58%, 56 of 97) and poorly differentiated carcinomas (84%, 21 of 25) than in noninvasive and well-differentiated carcinomas. Furthermore, a high frequency of Rd type was detected in the following advanced tumors: T3,4 tumors, 71% (22 of 31); tumors with extensive lymph node metastasis, 74% (29 of 39); and tumors with distant metastasis, 86% (19 of 22). These values were significantly higher compared with their counterparts. The expression of epidermal growth factor receptor tended to be positive in E-cad-positive tumors. However, no significant relationship was seen among E-cad expression, menopausal status, hormone receptor status, and DNA ploidy pattern. These results suggest that the reduction of E-cad expression may play an important role in invasion and metastasis of human breast cancer.
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              Role of chemotherapy for advanced/recurrent gastric cancer: an individual-patient-data meta-analysis.

              We conducted an individual-patient-data meta-analysis of the efficacy of chemotherapy on overall survival (OS) and progression-free survival (PFS) in advanced/recurrent gastric cancer (AGC). Our primary research question was whether the experimental arms of the trials included in the meta-analysis showed a benefit as compared with their corresponding control arms. MEDLINE (up to 2010), Cochrane Central Register of Controlled Trials, National Institutes of Health (NIH) trial registry and proceedings of major oncologic and gastrointestinal cancer meetings were searched. Randomised controlled trials for AGC closed to patient accrual before the end of 2006 were eligible. As of December 2010, individual patient data were available from 22 trials (4245 patients, representing 47% of the targeted data) of 55 eligible trials. The overall comparison of experimental arms with the corresponding control arms showed statistically significant differences in terms of both OS and PFS. Hazard ratio was 0.88 (95% confidence interval 0.82-0.94, P<0.0001) for OS and 0.81 (0.76-0.88, P<0.0001) for PFS. The results of the sub-analysis of adding a given chemotherapeutic agent to any chemotherapy confirm the results of the overall analysis, with a hazard reduction of 11% for OS (P<0.01) and 26% for PFS (P<0.0001). This meta-analysis of individual patient data shows that the additions of experimental chemotherapeutic agents to pre-existing control or standard regimens have produced a modest improvement in OS and PFS. Median survival remained below 1 year for all investigated chemotherapy regimens and none emerged as a clear standard. Copyright © 2012 Elsevier Ltd. All rights reserved.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                13 April 2015
                : 9
                : 2149-2157
                [1 ]College of Public Health, Xinjiang Medical University, Xinjiang, People’s Republic of China
                [2 ]First Department of Lung Cancer Chemotherapy, The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, People’s Republic of China
                [3 ]Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, People’s Republic of China
                [4 ]Department of Oncology, Traditional Chinese Medical Hospital Affiliated to Xinjiang Medical University, Xinjiang, People’s Republic of China
                [5 ]Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
                [6 ]School of Basic Medicine, Xinjiang Medical University, Xinjiang, People’s Republic of China
                Author notes
                Correspondence: Huiwu Li, School of Basic Medicine, Xinjiang Medical University, No 393, Xinyi Road, Urumqi, Xinjiang 830011, People’s Republic of China, Tel +86 991 781 9910, Email huiwulimd@ 123456yeah.net

                These authors contributed equally to this work

                © 2015 Zeng et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Pharmacology & Pharmaceutical medicine
                methylation,tumor suppressor gene,odds ratio
                Pharmacology & Pharmaceutical medicine
                methylation, tumor suppressor gene, odds ratio


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