KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients

AIM: To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer (CRC) and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.

AIM:To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer(CRC)and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.METHODS:KISS1 promoter methylation,mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction(PCR),real-time quantitative PCR and Western blotting,respectively,in 126 CRC tissues and 142 normal colorectal tissues.Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine(5-Aza-CdR).After treatment,KISS1 promoter methylation,KISS1 mRNA and protein expression and cell migration and invasion were evaluated.RESULTS:Hypermethylation of KISS1 occurred frequently in CRC samples(83.1%,105/126),but was infrequent in normal colorectal tissues(6.34%,9/142).Moreover,KISS1 methylation was associated with tumor differentiation,the depth of invasion,lymph node metastasis and distant metastasis(P<0.001).KISS1methylation was also associated with low KISS1 expression(P<0.001).Furthermore,we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.CONCLUSION:These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.