Objective: EPHB4, a member of the largest family of receptor tyrosine kinases (RTKs), is abnormal expression in several kinds of tumors , however its exact function has not been clearly shown. To detect the expression level of EPHB4 in tumor tissues, as well as the EPHB4 promoter region methylation status in tissues and peripheral blood from the patients with non-small cell lung cancer (NSCLC), and analyze the relationship between EPHB4 gene polymorphism and susceptibility of NSCLC. Reveal the relationship between EPHB4 gene and the occurrence and development of NSCLC in order to provide a new biomarker for the treatment and a new early diagnosis of NSCLC.Methods: By immunohistochemical method to detect the expression level of EPHB4 in tumor tissues. Methylation-specific PCR ( MSP ) and polymerase chain reaction-restriction fragment length polymorphism PCR (PCR-RFLP) was used for the detection of promoter region hypermethylation and polymorphism of EPHB4 gene in tissues and blood DNA from NSCLC patients and normal blood samples.Results: EPHB4 gene in cancer tissues was significantly lower than the level of normal organization.The incidence of the hypermethylation of EPHB4 promoter region in tumor tissues and blood from of NSCLC patients was 31.6% and 16.3 %, compared with normal tissue and blood samples there was a significant difference(P <0.05).Hypermethylation of EPHB4 gene promoter region may reduce the survival period (P<0.05). Polymorphism of EPHB4 may contribute to genetic susceptibility to NSCLC(P <0.05).Conclusion: As the first report, the expression level of EPHB4 in tumor tissues was lower, the hypermethylation of EPHB4 was significantly associated with the NCSLC, polymorphism of EPHB4 may associate with increased risk of NSCLC. EPHB4 may contribute to development process of NSCLC and play an important role in the hematogenous lung metastasis of adenocarcinoma and late squamous cell carcinoma. The detection might suggest that EPHB4 will be a promising biomarker in NSCLC.
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