Abstract:

Objective To detect the promoter methylation of human RUNT-related transcription factor 3 (RUNX3) gene in pancreatic carcinoma, and explore its clinical significance. Methods The methylation of promoter CpG island of 14 samples of normal pancreatic tissues, 56 samples of pancreatic carcinoma and adjacent tissues, 3 strains of pancreatic carcinoma cell lines (PANC1, CFPAC-1 and SW1990) and one strain of normal liver cell line (HL-7702) was detected by methylation-specific polymerase chain reaction (MSP). The expression of RUNX3 mRNA in pancreatic carcinoma cell lines before and after treatment with methylation inhibitor 5-Aza-2 deoxycytidine (5-Aza-cdR) was detected. The relationship between abnormal promoter methylation of RUNX3 gene and clinical characteristics of pancreatic carcinoma was analysed. Results Abnormal CpG island methylation in RUNX3 gene promoter was found in 29 cases of pancreatic carcinoma (29/56, 51.79%) and 6 cases of adjacent tissues (6/56, 10.71%), while no abnormal CpG island methylation of RUNX3 gene was found in normal pancreatic tissues. Abnormal CpG island methylation of RUNX3 gene was significantly related to differentiation grade (r=0.314, P=0.018) and lymph node metastasis (r=0.370, P=0.005). There was no expression or low expression of RUNX3 mRNA in pancreatic carcinoma cell lines (PANC1, CFPAC-1 and SW1990) before treatment with 5-Aza-cdR, while there was expression of RUNX3 mRNA in pancreatic carcinoma cell lines after treatment with 5-Aza-cdR. Conclusion Abnormal CpG island methylation of RUNX3 gene is found in pancreatic carcinoma tissues and pancreatic carcinoma cell lines. Promoter hypermethylation of RUNX3 is an important mechanism for low expression of RUNX3 in pancreatic carcinoma, and is significantly related to the differentiation grade and node metastasis.

Key words: pancreatic carcinoma, RUNX3 gene, methylation, methylation-specific polymerase chain reaction