CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients

Widschwendter, Andreas; Ivarsson, Lennart; Blassnig, Anya; Müller, Hannes M.; Fiegl, Heidi; Wiedemair, Annemarie; Müller‐Holzner, Elisabeth; Goebel, Georg; Marth, Christian; Widschwendter, Martin

doi:10.1002/ijc.11706

Cited by 102 publications

(89 citation statements)

References 23 publications

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“…Hypermethylation of CpG islands of promoter genes has been identified and associated with loss of expression of many potential key genes in cancer cells (8). Several studies have investigated the methylation status of genes in cervical cancer and evaluated their implication in carcinogenesis (17,18,(28)(29)(30)(31)(32)(33)(34)(35). In the present study we have investigated the methylation status of p16 INK4a and E cadherin gene promoters in four cervical cell lines, 20 normal HPV negative cervical swabs, and 22 cervical cancer specimens from Moroccan women.…”

Section: Discussionmentioning

confidence: 96%

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Attaleb¹,

W²,

Khyatti³

et al. 2009

oncol res

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Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16 INK4a and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16 INK4a and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5′ CpG island of the p16 INK4a and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16 INK4a and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16 INK4a gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.

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Section: Discussionmentioning

confidence: 96%

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Attaleb¹,

W²,

Khyatti³

et al. 2009

oncol res

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show abstract

“…Indeed, somatic CDH1 inactivation by mutation or promoter methylation is frequent in many human cancers (4,41). Furthermore, consistent with its biological function, hypermethylation of the CDH1 promoter has been shown to be a predictor of poor prognosis in a number of malignancies, including leukemia (42) and gastric (43), cervical (44), liver (45), and bladder (46) cancers. However, this finding has not been reported in lung cancer.…”

Section: Discussionmentioning

confidence: 96%

Aberrant Promoter Methylation Profile and Association with Survival in Patients with Non–Small Cell Lung Cancer

Gu¹,

Berman

Lu³

et al. 2006

Clinical Cancer Research

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Purpose: The aim of this study was to investigate the prognostic value of hypermethylation of tumor suppressor genes in patients with non-small cell lung cancer (NSCLC). Experimental Design: We examined the methylation status of nine genes in 155 tumors from patients with NSCLC using quantitative methylation-specific PCR. We analyzed the associations between gene methylation status and overall patient survival. Results: The methylation index, defined as the ratio between the number of methylated genes and the number of genes tested, was significantly higher in adenocarcinomas (0.38 F 0.20) than in squamous cell carcinomas (0.30 F 0.22; P = 0.027), in tumors from older patients (0.37 F 0.20) than younger patients (0.30 F 0.22; P = 0.040), and in tumors from heavier smokers (0.39 F 0.21) than lighter smokers (0.29 F 0.20; P = 0.042). In the Cox proportional hazards model, p16 methylation was associated with significantly poorer survival [hazard ratio, 1.95; 95% confidence interval (95% CI), 1.21-3.39]. Kaplan-Meier survival curves showed that patients with hypermethylated p16 had significantly shorter survival (median = 21.7 months) than patients without p16 hypermethylation (median = 62.5 months; P = 0.0001, log-rank test). Hypermethylation of CDH1 orTIMP3 gene was associated with significantly better survival with hazard ratios of 0.51 (95% CI, 0.29-0.90) and 0.59 (95% CI, 0.36-0.97), respectively. Joint analysis of these three genes showed a significant trend for poorer survival as the number of unfavorable events increased (P = 0.0007). Conclusion: Hypermethylation of multiple genes exhibited significant differential effect on NSCLC patient survival. Assessment of the effect of each methylated gene on survival is needed to provide optimal prognostic value.Both in the United States and around the world, lung cancer is the leading cause of cancer death in men and women, with a 5-year survival rate of only 15%, a statistic that has changed very little over the past two decades (1). This dismal survival could be improved through earlier detection or through identification of prognostic markers, which could identify subsets of patients with worse prognosis who might benefit from a more aggressive treatment strategy.It is now well established that epigenetic changes (i.e., heritable changes in gene expression without alterations in the primary DNA sequence of a gene; refs. 2, 3) play an important role in cancer development. The major epigenetic aberration in cancer development is inactivation of tumor suppressor genes (TSG) through hypermethylation of CpG islands in their promoter regions. The spectra and frequency of TSG inactivation at the CpG islands vary from cancer to cancer (3 -5). The distinct profile and varying levels of TSG methylations among different cancers, coupled with a sensitive methylation-specific PCR (MSP) technique, have shown promise as a tool for the early detection and diagnosis of cancer and for determining prognosis (5 -9).A number of genes are heavily methylated in non -small cell...

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“…The circulating DNA has a similar methylation status to that found in tumours, therefore methylated DNA in serum may potentially be used as a novel, convenient and non-invasive biomarker for patients with cancer. 21,25,29 The methylation status of the CDH13 gene promoter in serum samples from patients with bladder TCC and normal healthy volunteers was systematically investigated in the present study. CDH13 promoter methylation was detected in 39 (30.7%) patients with bladder TCC, but was not observed in the healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance ofCDH13Promoter Methylation in Serum Samples from Patients with Bladder Transitional Cell Carcinoma

Lin

Sun

et al. 2011

J Int Med Res

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H-cadherin (CDH13; also known as T-cadherin), which functions as a tumour suppressor, is frequently silenced by promoter methylation in human cancers including bladder transitional cell carcinoma (TCC). This study investigated the clinical significance of methylation of the CDH13 gene promoter in serum from patients with bladder TCC. Methylation status of CDH13 in serum samples from 127 patients with primary bladder TCC and 41 healthy volunteers (controls) was examined by methylation-specific polymerase chain reaction. CDH13 methylation was found in 39 patients with bladder TCC (30.7%) but in no controls. CDH13 methylation was significantly associated with advanced tumour stage, high-grade tumour, large tumour size, tumour recurrence and poor prognosis. The results suggested that CDH13 methylation in serum may be a potential predictive biomarker for malignancy in bladder TCC, and an independent pre-therapeutic predictor of outcome. Demonstration of CDH13 methylation in serum may facilitate in the prediction of which patients require more aggressive additional post-operative systemic therapy.

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CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients

Cited by 102 publications

References 23 publications

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Aberrant Promoter Methylation Profile and Association with Survival in Patients with Non–Small Cell Lung Cancer

Clinical Significance ofCDH13Promoter Methylation in Serum Samples from Patients with Bladder Transitional Cell Carcinoma

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