CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer

Liu, Jian; Sun, Xin; Qin, Sida; Wang, Huangzhen; Du, Ning; Li, Yanbo; Pang, Yamei; Wang, Cuicui; Xu, Chongwen; Ren, Hong

doi:10.3892/ol.2016.4274

Cited by 59 publications

(45 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our study indicated that the CDH1 methylation rate in CXPA was 67.57% (25/37). This rate is similar to that of many other tumors, including primary lung cancer (88%) (30), breast carcinoma (65-95%) (7,10,31,32) and colorectal carcinoma (52%) (33). We found that DNA methylation preferentially occurred in the first four CpG islands compared with the other CpG islands.…”

Section: Discussionsupporting

confidence: 86%

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

Xia

et al. 2017

Int J Oncol

View full text Add to dashboard Cite

The role of promoter methylation in the inactivation of E‑cadherin (CDH1) in salivary carcinoma ex pleomorphic adenoma (CXPA) is unknown. The objective of this study was to determine the role and potential clinical implications of CDH1 promoter methylation in salivary CXPA. The CDH1 promoter methylation status was determined by bisulfite sequencing PCR in 37 primary CXPA tissues and 2 CXPA cell lines. E‑cadherin expression levels were determined by immunohistochemical analysis of each tumor. E‑cadherin protein levels and CDH1 mRNA levels were examined by immunoblotting and quantitative real-time PCR, respectively, in 2 CXPA cell lines. Cells were treated with 5‑Aza-dC or TGF‑β1 to test the influence of promoter methylation on CDH1 mRNA and protein expression. Associations between CDH1 molecular alterations and patients' clinicopathologic characteristics and prognosis were statistically evaluated. CDH1 promoter hypermethylation was detected in 21 of 37 tumors (56.76%). Of these 37 tumors, 13 tumors (35.14%) showed low E‑cadherin expression. Tumors that had CDH1 promoter methylation had a histological tendency toward luminal differentiation (P=0.004), high tumor grade (P=0.005), high T stage (P=0.024) and high TNM stage (P=0.038) compared with tumors that did not. The two CXPA cell lines exhibited an inverse relationship between CDH1 promoter methylation status and CDH1 mRNA and protein expression. Treatment of the hypermethylated cell line with 5‑Aza-dC restored CDH1 mRNA and E‑cadherin protein expression. The induction of hypermethylation by TGF‑β1 resulted in the repression of CDH1 mRNA and protein expression. CDH1 is commonly silenced in CXPA through promoter methylation. CDH1 methylation is closely related to tumor cell differentiation, histological grade, lymph node metastasis and advanced TNM stage, indicating that CDH1 methylation may play a role in the initiation and progression of CXPA.

show abstract

Section: Discussionsupporting

confidence: 86%

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

Xia

et al. 2017

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Specifically, CDH1 , which encodes the cell adhesion protein E-cadherin, is an important TSG 55. Studies have shown that loss of CDH1 expression by promoter hypermethylation is involved in several types of cancer, including colorectal,56 lung,57 breast,23 and gastric cancers 58. This meta-analysis was done to resolve some of the inconsistent reports of the association between CDH1 promoter methylation and HNSCC 15,16…”

Section: Discussionmentioning

confidence: 99%

“…There has been increasing evidence showing that loss of CDH1 expression is involved in tumor cell invasion and metastasis in cancer, including HNSCC 20–22. Several studies have found that promoter methylation of CDH1 may lead to transcriptional inactivation of CDH1 and that this mechanism is involved in several types of malignancy, including breast,23 gastric,24 and colorectal cancers,25 and HNSCC 26,27…”

Section: Introductionmentioning

confidence: 99%

The association, clinicopathological significance, and diagnostic value of <em>CDH1</em> promoter methylation in head and neck squamous cell carcinoma: a meta-analysis of 23 studies

Shen

Zhou

et al. 2016

OTT

View full text Add to dashboard Cite

Epithelial cadherin (encoded by the CDH1 gene) is a tumor suppressor glycoprotein that plays a role in the invasion and metastasis of human cancers. As previous studies regarding the association between CDH1 promoter methylation and head and neck squamous cell carcinoma (HNSCC) have yielded inconsistent conclusions, a meta-analysis was performed. A systematic literature review was undertaken from four databases: PubMed, Embase, Google Scholar, and Web of Science. Finally, a total of 23 studies (including 1,727 cases of HNSCC and 555 normal controls) were included in the present study. Our results showed that the frequency of CDH1 promoter methylation in HNSCC was statistically greater than in controls (odds ratio [OR] =5.94, 95% confidence interval [CI]: 3.36–10.51, P<0.001). In reported cases of HNSCC, CDH1 promoter methylation was statistically associated with tumor stage (OR =0.46, 95% CI: 0.27–0.78, P=0.004) and a history of alcohol consumption (OR =6.04, 95% CI: 2.41–15.14, P<0.001). Moreover, the sensitivity, specificity, and area under the curve of the summary receiver operator characteristic for the included studies were 0.50 (95% CI: 0.4–0.61), 0.89 (95% CI: 0.79–0.95), and 0.74 (95% CI: 0.70–0.78), respectively. In conclusion, our meta-analyses indicated that CDH1 promoter methylation was associated with HNSCC risk, and may be utilized as a valuable diagnostic biomarker for HNSCC.

show abstract

“…Two markers were both significantly associated with poor and improved outcome in separate studies [54,75,78,91]. Five markers showed a significant relation to poor outcome in one study, while other studies looking into the same marker found no correlation [44,57,58,65,83]. Finally, four markers showed no significant relation to disease outcome in any study [48,63,66,68,70,88,92,95].…”

Section: Prognostic Marker Findingsmentioning

confidence: 91%

“…Two alternative promotor sites were analysed in these studies; for both alternative promotors, significant correlation to poor survival was found. Three studies reported on CDH1 methylation in relation to disease outcome [49,50,58]. Two studies identified a statistically significant correlation between CDH1 hypermethylation and poor disease outcome.…”

Section: Prognostic Marker Findingsmentioning

confidence: 99%

Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review

et al. 2020

View full text Add to dashboard Cite

Background: In patients with hormone receptor-positive breast cancer, differentiating between patients with a low and a high risk of recurrence is an ongoing challenge. In current practice, prognostic clinical parameters are used for risk prediction. DNA methylation markers have been proven to be of additional prognostic value in several cancer types. Numerous prognostic DNA methylation markers for breast cancer have been published in the literature. However, to date, none of these markers are used in clinical practice. Methods: We conducted a systematic review of PubMed and EMBASE to assess the number and level of evidence of published DNA methylation markers for hormone receptor-positive breast cancer. To obtain an overview of the reporting quality of the included studies, all were scored according to the REMARK criteria that were established as reporting guidelines for prognostic biomarker studies. Results: A total of 74 studies were identified reporting on 87 different DNA methylation markers. Assessment of the REMARK criteria showed variation in reporting quality of the studies. Eighteen single markers and one marker panel were studied in multiple independent populations. Hypermethylation of the markers RASSF1, BRCA, PITX2, CDH1, RARB, PCDH10 and PGR, and the marker panel GSTP1, RASSF1 and RARB showed a statistically significant correlation with poor disease outcome that was confirmed in at least one other, independent study. Conclusion: This systematic review provides an overview on published prognostic DNA methylation markers for hormone receptor-positive breast cancer and identifies eight markers that have been independently validated. Analysis of the reporting quality of included studies suggests that future research on this topic would benefit from standardised reporting guidelines.

show abstract

CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer

Cited by 59 publications

References 41 publications

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

Promoter hypermethylation may contribute to E‑cadherin repression in the human salivary carcinoma ex pleomorphic adenoma

The association, clinicopathological significance, and diagnostic value of <em>CDH1</em> promoter methylation in head and neck squamous cell carcinoma: a meta-analysis of 23 studies

Prognostic DNA methylation markers for hormone receptor breast cancer: a systematic review

Contact Info

Product

Resources

About