The Methylation Status Of E-cadherin Gene In Non-small Cell Lung Cancer And Its Clinical Significance

Objective:①First, our aim is to explore mRNA expression levels of E-cadherin genes in tumor and the corresponding paracarcinoma tissues from patients with non-small lung cancer (NSCLC) and its clinical implication.②Second,explore the relationship between downregulation of E-cadherin mRNA expression and methylation status of its promoter region.Methods:A nested methylation specific PCR (MSP) was performed followed by bisulfite DNA sequencing to examine CpG methylation within the5’CpG island of E-cadherin in37tumor and paired normal tissue specimens from patients with primary NSCLC. Then, real-time quantitative PCR analysis was carried out to determine the level of E-cadherin mRNA (excluding2samples with unavailable mRNA).Results:Of thirty-seven cases,12(32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. No significance difference was found between methylated promoter of E-cadherin and clinicopathological parameters. In addition, reduction of E-cadherin mRNA level was observed in11of12(91.7%) tumor tissues carrying methylation. However, only10(43.5%) cases displayed reduced mRNA levels in the rest of tumor tissues from other23cases (excluding2samples with unavailable mRNA) without methylation event. Downregulation of E-cadherin expression was found to correlate significantly with promoter methylation of this gene. As a result, there were three cancer-specific methylated sites-89,-65and-55, which are upstream close to the translation start site of the E-cadherin gene.Conclusion:As the report in NSCLC, three methylated CpG sites were identified in the region under the present investigation. Our results provide strong evidence for supporting the idea that the methylation status of E-cadherin gene contribute clearly to the reduced expression of E-cadherin mRNA and may play a potential role in the development and progression of NSCLC.