Methylation Of FHIT Gene And SLIT2 Gene In Plasma From Hepatocellular Carcinoma Patients

Objective To detect the aberrant methylation in the promoter of FHIT gene and SLIT2 gene in peripheral plasma from hepatocellular carcinoma (HCC)patients and its possible clinical application in molecular diagnosis of HCC. Methods The methylation status of FHIT gene and SLIT2 gene in peripheral plasma from 36 patients with HCC and 10 healthy donor controls were detected by methylation-specific polymerase chain reaction (MSP).The correlation of methylation status in plasma and clinicopathological features was analyzed. Results Of the 36 plasma samples,the frequency of hypermethylation of FHIT was 50.0%(18?36)and the frequency of hypermethylation of SLIT2 was 27.8%(10?36), the methylation of either one could be detected in 61.1%(22/36)plasma samples ; Promoter hypermethylation of FHIT gene and SLIT2 gene was not found in plasma samples from the healthy donor controls . The aberrant methylation of FHIT gene and SLIT2 gene in peripheral plasma had no correlation to patients'clinicopathological features such as gender, age, HBV infection, hepatic cirrhosis, tumor size, AFP level, pathological grade, staging, carcino-embolus and recurrence. The sensitivity of AFP detection (≥20μg/L) in 36 HCC patients was 61.1% ( 22/36 ) . In 14 patients whose AFP < 20μg/L, the frequency of hypermethylation of FHIT was 42.8%(6?14)and the frequency of hypermethylation of SLIT2 was 28.6%(4?14); the methylation of either one could be detected in 64.3%(9?14)plasma samples of the patients . The sensitivity of AFP detection altogether with FHIT gene and SLIT2 gene promoter hypermethylation detection is 86.1%, better than that of AFP detection alone(x2=5.79, P<0.05). Conclusions The detection of methylation status of FHIT gene and SLIT2 gene in peripheral plasma may be a potential molecular diagnostic factor of HCC.The methylation status had no correlation to patients'clinicopathological features. AFP detection altogether with FHIT gene and SLIT2 gene promoter hypermethylation detection can improve the sensitivity in HCC diagnosis.