Transcriptional Expression And Promoter Hypermethylation Of RASSF1A In Gastric Carcinomas

Gastric cancer was malignant tumor which severity influence human health. But the etiological factor of gastric cancer was not clear and curative effect of gastric cancer was far to satisfaction up to now. Great deal of findings suggested that activation of oncogenes or inactivation of tumor suppressor genes is one of the key steps in the multistep molecular processes of tumourigenesis. Previous research has noticed that Heterozygosity (LOH) and deletion of gene fragment in 3p is a common phenomenon in many types of malignant tumors. Those predict that this region has tumor suppressor gene. In 2000, Dammann isolated a RAS association domain family 1, RASSF1, which was located in the 120-kb region of minimal homozygous deletion at 3p21.3 in lung cancer. The RASSFI gene encoded three major transcripts, RASSFIA, RASSF1B and RASSFIC, which was produced by alternative promoter selection and different message RNA (mRNA) splicing. RASSFIA was frequently inactivated in lung cancer cell lines by promoter hypermethylation. There are only a few researches of RASSFIA in gastric carcinoma. In the present study, we used RT-PCR to evaluate the transcriptional expression of RASSFIA and used MSP (Methylation-specific PCR) method to detect the methylation status of RASSFIA promotor CpG island in gastric cancer and corresponding non-cancerous tissues to clarify the possible role of RASSFI A in gastric carcinoma. Results:1. RASSFIA mRNA were all shown in 48 non-cancerous tissues, It was found that there was significantly lower in the gastric cancer tissues (p<0.001).2. The expression of RASSFIA was consistent with the degree of differentiation in the gastric cancer (p<0.001). Moreover, the expression of RASSFIA was correlated well with classification the depth of infiltration (p<0.001) and lymphnode metastasis (p<0.001). It was not correlated with sex, age and histological type (p>0.05).3. We found no hypermethylation of RASSF1A in 48 non-cancerous tissues. But hypermethylation of RASSFIA was found in 38.9% of gastric cancer tissues.4. We did not found that the methylation status of RASSFIA promoter was associated with the age and gender of gastric cancer (p>0.05). And there was a statistically significant correlation between the lymph node metastasis (p>0.05). But the methylation status of RASSFIA was statistically associated with the degree of differentiation and the depth of infiltration in the gastric cancer tissues (p<0.05).Conclusion:Our findings suggested that the promoter hypermethylation of RASSFIA may be a useful molecular marker for early detection of gastric carcinoma. Furthermore, RASSFIA methylation could play an important role in the development of gastric cancer. So we suggested that the promoter hypermethylation may be valuable in the diagnosis and prognostic of gastric cancer.