Abstract
Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinases ErbB family and it is found to be overexpressed in gastric cancer. However, the mechanism of the regulation of the EGFR expression is still unknown. We used the Sequenom EpiTYPER assay to detect the methylation status of the EGFR promoter in normal and tumour tissues of 30 patients with gastric cancer. We also carried out quantitative real time PCR (qPCR) to detect the expression level of EGFR in our 30 patients. Notably, increased methylation level at EGFR promoter was found in tumour tissues than the corresponding adjacent noncancerous. In both Region I DMR and Region II DMR detected in our study, tumor tissues were significantly hypermethylated (P = 2.7743E−10 and 2.1703E−05, respectively). Region I_⊿CpG_2 was also found to be associated with the presence of distant metastasis (P = 0.0323). Furthermore, the results showed a strongly significant association between the relative EGFR expression and the EGFR methylation changes in both Region I and Region II (P = 0.0004 and 0.0001, respectively). Our findings help to indicate the hypermethylation at EGFR promoter in gastric cancer and it could be a potential epigenetic biomarker for gastric cancer status and progression.
Highlights
Gastric cancer is the third most common malignant tumor and the second most frequent cause of cancer death worldwide[1]
Epidermal growth factor receptor (EGFR) belongs to the family of receptor tyrosine kinases (RTK) ErbB, which consisting of HER1/ EGFR/ErbB1, HER2/Neu/ErbB2, HER3/ErbB3 and HER4/ErbB43
We carried out quantitative real time Polymerase chain reaction (PCR) to detect the expression level of EGFR to see the relationship between the EGFR methylation changes and the relative EGFR expression
Summary
Gastric cancer is the third most common malignant tumor and the second most frequent cause of cancer death worldwide[1]. EGFR expression in cancer cells is tightly controlled, but the mechanism of the regulation of the EGFR expression is not fully studied. Epigenetic regulation is a biological mechanism by which gene expression is modulated through DNA methylation and histone modifications. Understanding of the mechanisms underlying promoter methylation status and the regulation of EGFR expression might lead to the development of useful clinical biomarkers. We used the Sequenom EpiTYPER assay to study the relationship between the methylation changes of the EGFR promoter and gastric cancer as well as its clinical characteristics such as histology differentiation, histologic grading, infiltration, TNM stage, and distant metastasis. We aimed to investigate whether methylation status of the EGFR promoter correlates with malignancy and patient outcome in gastric cancer
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