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

Abstract

BackgroundCDH1 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.MethodsA 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.ResultsA 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).ConclusionThe 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.

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

“…E-cadherin, as a critical molecular feature of EMT, was downregulated and indicated as a tumor suppressive role in various carcinomas [25,28]. Zeng et al [29] elucidated that loss of E-cadherin expression or function could initiate the activation of transcription factors which are associated with EMT, finally resulting in cancer metastasis. Reduced expression of E-cadherin was correlated with infiltrative tumor growth pattern and lymph node metastasis in colorectal cancer [30][31][32].…”

Rare Variants in the Epithelial Cadherin Gene Underlying the Genetic Etiology of Nonsyndromic Cleft Lip with or without Cleft Palate

“…), we speculate that a common underlying molecular mechanism could explain both phenotypes. Penetrance of CDH1 germline mutations implicated in HDGC depends on a second hit, which frequently occurs via promoter hypermethylation of the nonmutated allele, possibly triggered by environmental factors [Oliveira et al., ; Zeng et al., ]. In this regard, a lifetime exposure to such factors would be in agreement with the higher penetrance in HDGC (80%) [Pharoah et al., ], as compared to NSCL/P (47%).…”

PLOD2 as a potential regulator of peritoneal dissemination in gastric cancer

“…Various oncoproteins reportedly contribute to peritoneal dissemination of GC, which respectively affect angiogenesis, survival in the microenvironment and epithelial–mesenchymal transition (EMT) . Hypoxia and hypoxia‐inducible factor‐1 and ‐2 (HIF‐1 and HIF‐2) have been studied as promoters of metastasis in various tumors .…”