Methylation of RASSF1A gene promoter and the correlation with DNMT1 expression that may contribute to esophageal squamous cell carcinoma

World Journal of Surgical Oncology

Jianfei Song¹  Xiaoyan Feng¹  Feng Lin¹  Lifei Zhang¹  Haiyong Wang¹  Angui Li¹  Xiaolin Sun¹  Kui Ma¹  Zhenzong Du¹ 

[1] Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China

关键词: RASSF1A;    DNA methyltransferase 1;    DNA methylation;    Esophageal squamous cell carcinoma;   

Others  :  1175223
DOI  :  10.1186/s12957-015-0557-y

 received in 2014-11-05, accepted in 2015-03-23,  发布年份 2015

【 摘 要 】

Background

Esophageal squamous cell carcinoma is one of the most common malignancies in the world. Studies have confirmed that there are many genes abnormally hypermethylated in esophageal squamous cell carcinoma. The objective is to detect methylation of the RASSF1A gene promoter and the expression of the DNA methyltransferase 1 (DNMT1) protein in esophageal cancer tissue and discuss their relationship with esophageal squamous cell carcinoma.

Methods

The CpG island methylation status of RASSF1A genes were analyzed in 100 cases of tumor specimens as well as their adjacent tissues which was used for methylation-specific polymerase chain reaction (MSP). The expression of DNMT1 protein was determined by immunohistochemistry. Difference between measurement data and categorical data was compared through analysis of t test and chi-square test. All the statistics were taken with a bilateral test. The difference was statistically significant (P < 0.05).

Results

The promoter methylation of the RASSF1A gene promoter has been detected in 45 out of 100 (45%) esophageal squamous carcinoma cases, while methylation of RASSF1A gene has been detected in 2 out of 100 adjacent normal tissues (2%). The RASSF1A gene promoter was highly methylated in cancer tissues, and there were significant differences between normal esophagus tissues and esophageal squamous carcinoma (P < 0.05). The expression of DNMT1 protein has been detected in 61 out of 100 (61%) esophageal squamous carcinoma cases, including 41 cases in the above 45 methylated samples of RASSF1A gene promoter, and none in adjacent tissues. DNMT1 proteins are highly expressed in cancer tissues, and there were significant differences (P < 0.05). In positive cases for methylation of RASSF1A, the DNMT1 protein had been detected in 41 out of 45 (91%), while in non-methylated cancer cases, 20 out of 55(36.3%), and the difference is significant (P < 0.05).

Conclusions

Esophageal squamous carcinoma tumorigenesis may be related with hypermethylation of DNMT1 and RASSF1A promoter CpG island due to their high expression and also their hypermethylation.

【 授权许可】

   
2015 Du et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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