Promoter hypermethylation of the RUNX3 gene in colorectal carcinogenesis and its prognostic significance / 中华普通外科杂志

ABSTRACT

ObjectiveToinvestigateRUNX3genepromoter methylationincolorectal carcinogenesis and its prognostic significance. MethodsThe 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.ResultsThe 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 wasanindependentprognosticfactoramongthefactorsanalyzed(P=0.033 ).ConclusionsRUNX3 methylation is important genetic event in colorectal carcinogenesis,possibly related to protein downregulation,and an independent prognostic factor for colorectal carcinoma.