Association Between p16, hMLH1 and E-cadherin Promoter Hypermethylation and Intake of Local Hot Salted Tea and Sun-dried Foods in Kashmiris with Gastric Tumors

Mir, Manzoor Ur Rahman; Shabir, Nadeem; Wani, Khursheed Alam; Shaff, Sheikh; Hussain, Ishraq; Banday, Manzoor Ahmad; Chikan, Naveed Anjum; Bilal, Sheikh; Aejaz, Sheikh

doi:10.7314/apjcp.2012.13.1.181

Cited by 14 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous genes have been found to be methylated in GC, including hMLH1, p16, RUNX3, DAPK1, SFRP2 and RNF180. hMLH1 encodes DNA repair proteins and is closely associated with poor prognosis of GC patients; the frequency and specificity were found to be 8.6–80 and 4.1–80%, respectively (17–19). P16 inhibits cell cycle progression, and has been found to correlate with poor tumor differentiation, lymph node metastasis and poor survival.…”

Section: Discussionmentioning

confidence: 99%

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Xie

Sun

et al. 2014

Oncology Letters

View full text Add to dashboard Cite

Gastric cancer (GC) is one of the most frequently diagnosed malignancies in East Asia, particularly in China, and remains the second leading cause of cancer-associated mortality worldwide. However, no effective plasma biomarkers have been identified for the diagnosis of patients with GC. The aim of this study was to investigate the DNA methylation status of the ring finger protein 180 (RNF180), secreted frizzled-related protein 2 (SFRP2) and death-associated protein kinase 1 (DAPK1) genes in the plasma samples of 57 GC patients and 42 control individuals with no malignant disease, and to evaluate the clinical utility of these makers. A significantly higher level of methylation was observed in the plasma DNA of GC patients when compared with that of controls for the three genes investigated (RNF180, 57.89% vs. 23.81%; DAPK1, 49.12% vs. 28.57%; and SFRP2, 71.93% vs. 42.86%). No association was identified between the DAPK1 or SFRP2 methylation level in the plasma DNA and the clinicopathological parameters of patients. Notably, RNF180 methylation was found to positively correlate with tumor size (P=0.018), histological type (P=0.025), TNM stage (P=0.002), lymph node metastasis (P=0.008) and distant metastasis (P=0.018). Overall, 50 cancer patients (87.72%) exhibited methylation of at least one of the three markers, while 26 normal subjects presented methylation in plasma DNA [specificity, 38.1%; odds ratio (OR), 4.4]. The combined use of RNF180 and SFRP2 as methylation markers appeared to be the most preferable predictor with regard to predictive power and cost-performance (OR, 5.57; P=0.0002). The results of the present study indicate that aberrant promoter methylation of genes in the plasma may be detected in a substantial proportion of GC patients and thus, these genes must be evaluated in the screening and surveillance of GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Xie

Sun

et al. 2014

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…The cytoplasmatic terminus of the E-cadherin molecule has been shown to be linked to the actin cytoskeleton via α-catenin and β-catenin (Cavallaro and Christofori, 2004). In malignant tumors in general, E-cadherin and catenins are strongly expressed in low grade tumors that maintain their cell adhesiveness and are less invasive, whereas their expressions are reduced in high grade tumors which have lost their intercellular adhesion and show strong invasive behavior (Mir et al, 2012;Yuan et al, 2012). Alterations in E-cadherin expression have been related in several cancer types including breast cancer with pathological features such as poor tumoral differentiation, infiltrative growth, lymph node metastasis and decreased patient survival (Oka et al, 1992;Hirohashi, 1998;Yoshida et al, 2001;Brock et al, 2003;Yuan et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p= 0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

show abstract

“…Based on above selection criteria, 39 studies were included in our research. Twenty-three of them (Suzuki et al, 1999 ; Bevilacqua and Simpson, 2000 ; Leung et al, 2001 ; Oue et al, 2001 , 2006 ; Sakata et al, 2002 ; Kang et al, 2003 ; Etoh et al, 2004 ; An et al, 2005 ; Hong et al, 2005 ; Shibata et al, 2006 ; Kolesnikova et al, 2008 ; Poplawski et al, 2008 ; Zhang et al, 2008 ; Ksiaa et al, 2009 ; Hiraki et al, 2010 ; Mikata et al, 2010 ; Mir et al, 2012 ; Wani et al, 2012 ; Song et al, 2013 ; Xiong et al, 2013 ; Jin et al, 2014 ; Liu and Yang, 2015 ) evaluated the association between hMLIH1 promoter methylation and gastric cancer risk, including 2,182 cases and 2,319 controls; 27 of them (Fleisher et al, 1999 ; Leung et al, 1999 ; Suzuki et al, 1999 ; Toyota et al, 1999 ; Pinto et al, 2000 ; Nakajima et al, 2001 ; Oue et al, 2001 , 2003 ; Sakata et al, 2002 ; Fang et al, 2003 ; Sugai et al, 2004 ; Wu et al, 2004 ; An et al, 2005 ; Hong et al, 2005 ; Kim et al, 2005 , 2010 ; Nan et al, 2005 ; Kolesnikova et al, 2008 ; Ferrasi et al, 2010 ; Hiraki et al, 2010 ; Mikata et al, 2010 ; Alves et al, 2011 ; Song et al, 2013 ; Xiong et al, 2013 ; Jin et al, 2014 ; Moghbeli et al, 2014 ; Kawanaka et al, 2016 ) with 2,713 patients investigated the associations of hMLIH1 methylation with clinicopathological features including lymph node metastasis, Lauren's histological type, microsatellite status, Helicobacter pylori (HP) infection status, and hMLH1 protein expression in gastric cancer patients. The flow chart (Figure…”

Section: Resultsmentioning

confidence: 99%

Association Between hMLH1 Promoter Methylation and Risk of Gastric Cancer: A Meta-Analysis

Shi

2018

Front. Physiol.

View full text Add to dashboard Cite

Background: Human mutL homolog 1 (hMLH1) is located on chromosome 3q21-23. As a classic tumor suppressor gene, many researchers have studied the association between hMLH1 promoter methylation and gastric cancer, but their conclusions were not always consistent. Therefore, we performed a meta-analysis to make a more integrated and precise estimate of the associations.Method: PubMed, EMBASE, and Cochrane Library were retrieved without language restrictions. Data were analyzed by Review Manager 5.2 and Stata 12.0 software. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the statistical associations.Result: A total of 39 studies published before January 20, 2018 were included in this study. The results indicated that the frequency of hMLH1 promoter methylation in gastric cancers was substantially higher than that in non-cancer controls (OR = 7.94, 95%CI = 4.32–14.58, P < 0.001). Furthermore, hMLH1 promoter methylation had considerable associations with lymph node metastasis, microsatellite instability (MSI), and low expression of hMLH1 protein (OR = 1.53, 95%CI = 1.04–2.26, P = 0.03; OR = 15.33, 95%CI = 9.26–25.36, P < 0.001; OR = 37.86, 95%CI = 18.03–79.50, P < 0.001, respectively). No association was found between hMLH1 promoter methylation and Lauren classification or Helicobacter pylori (HP) infection status.Conclusion: The present study provides evidence that promoter methylation of hMLH1 is a major causative event in the occurrence and development of human gastric cancer.

show abstract

Association Between p16, hMLH1 and E-cadherin Promoter Hypermethylation and Intake of Local Hot Salted Tea and Sun-dried Foods in Kashmiris with Gastric Tumors

Cited by 14 publications

References 30 publications

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Detection of aberrant promoter methylation of RNF180, DAPK1 and SFRP2 in plasma DNA of patients with gastric cancer

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Association Between hMLH1 Promoter Methylation and Risk of Gastric Cancer: A Meta-Analysis

Contact Info

Product

Resources

About