A Systematic Analysis of the Relationship of CDH13 Promoter Methylation and Breast Cancer Risk and Prognosis.

BACKGROUND

CDH13 (cadherin 13) is a special cadherin cell adhesion molecule, and the methylation of its promoter causes inactivation in a considerable number of human cancers. To explore the association between CDH13 promoter methylation and breast cancer risk and prognosis, we systematically integrated published articles to investigate the diagnostic performance of the CDH13 methylation test for breast cancer. An independent DNA methylation microarray dataset from The Cancer Genome Atlas project (TCGA) project was used to validate the results of the meta-analysis.

METHODS

The relevant literature was searched using the PubMed, Cochrane Library, Web of Science and Google Scholar databases for articles published in English up to May 2015. Data were analyzed using random effect or fixed effect models. The effect sizes were estimated by measuring an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI). A chi-squared based Q test and sensitivity analysis were performed to examine the between-study heterogeneity and the contribution of single studies to the final results, respectively. Funnel plots were constructed to evaluate publication bias.

RESULTS

Seven hundred and twenty-six breast tumor samples and 422 controls were collected from 13 published studies. The data from the TCGA set include both tumor and normal samples. A significant association was observed between CDH13 promoter methylation and breast cancer, with an aggregated OR equal to 13.73 (95%CI: 8.0923.31, z = 9.70, p<0.0001) as measured using the fixed effect model and 14.23 (95%CI: 5.0640.05, z = 5.03, p<0.0001) as measured using a random effect model. The HR values were calculated as 0.77 (95%CI: 0.272.21, z = -0.49, p = 0.622) and 0.38 (95%CI: 0.091.69, z = -1.27, p = 0.20) for overall survival (OS) and disease-free survival (DFS), respectively, using the random effect model. This result indicated that breast cancer patients with CDH13 promoter methylation correlated non-significantly with prognosis and is therefore similar to the findings of the TCGA project.

CONCLUSIONS

The methylation status of CDH13 promoter was strongly associated with breast cancer risk. However, CDH13 promoter methylation was not significantly related to the OS and DFS of breast cancer and may have limited prognostic value for breast cancer patients.