Promoter hypermethylation of the RUNX3 gene in colorectal carcinogenesis and its prognostic significance

Objective To investigate RUNX3 gene promoter methylation in colorectal carcinogenesis and its prognostic significance. Methods The protein expression of RUNX3 was detected by immunohistochemistry and the methylation status of the RUNX3 was determined by methylation-specific PCR (MSP) in colorectal normal mucosa and cancer tissue from 65 patients,and adenoma from 28 patients.5-year overall survival rate was analysed according to RUNX3 methylation status from cancer patients.Kruskal-Wallis rank sum test,x2 or Fisher's exact test,Log-rank test and multivariable Cox regression analysis were used for statistical analysis.Results The protein expression of RUNX3 gene in adenoma and cancer was 85％ (24/28) and 52％ (34/65),significantly lower than that in normal mucosa 94％ (61/65)( x2 =4.328,P =0.037 ; x2 =16.675,P =0.000),the difference between adenoma and cancer tissue was no statistic significance (x2 =3.266,P =0.071 ).No case showed RUNX3 methylation in normal mucosa,methylation rates in adenoma and cancer tissue were 21％ (6/28) and 35％ (23/65),significantly higher than in normal mucosa (P =0.000 ),but there was no statistic significance between adenoma and cancer tissue (x2 =1.766,P =0.183).The protein expression rate with RUNX3 methylation was 67％ (4/6) in adenoma,unmethylation 91％ (20/22) (P =0.191 ).The protein expression rate with RUNX3 methylation was 26％ (6/23) in cancer,unmethylation was 88％ (28/32).The presence of RUNX3 methylation was related to loss of protein ( x2 =9.810,P =0.002 ).5-year total survival rate with methylation in cancer was significantly lower with unmethylation ( x2 =5.87,P =0.016 ).Multivariate analysis showed RUNX3 methylayion was an independent prognostic factor among the factors analyzed (P =0.033 ).Conclusions RUNX3 methylation is important genetic event in colorectal carcinogenesis,possibly related to protein downregulation,and an independent prognostic factor for colorectal carcinoma. Key words: Colorectal neoplasms; DNA methylation; Gene; Tumor marker, biological; Prognosis