FHIT And RASSF1A Promoter Hypermethylation In Plasma And Tumor Tissue Of Patients With Hepatocellular Carcinoma

Objective To detect the aberrant methylation in the promoter of FHIT gene、RASSF1A gene in peripheral plasma and tumor tissue from hepatocellularcarcinoma(HCC) patients and its possible clinical application of HCC． MethodsThe methylation status of FHIT gene、RASSF1A gene in peripheral plasma and tumortissue from36patients with HCC and10healthy donor controls were detected bymethylation-specific polymerase chain reaction(MSP). The correlation betweenmethylation status in plasma, tumor tissue and clinicopathological features wasanalyzed. Results The frequency of promoter methylation of FHIT [27/36,75%for tissue and19/36,52.8%for plasma], the correlation coefficient between tissue andplasma: r=0.482（P=0.003）.The frequency of promoter methylation of RASSF1A[30/36,83.3%for tissue and22/36,61.1%%for plasma], the correlation coefficientbetween tissue and plasma: r=0.561（P=0.0004）. Promoter hypermethylation of FHITgene and RASSF1A gene was not found in plasma and tumor tissue samples from thehealthy donor controls. The aberrant methylation of FHIT, RASSF1A gene in theplasma and tumor tissue had no correlation to the patients’ clinicopathologicalfeatures such as gender, age, HBV/HCV infection, hepatic cirrhosis, tumor size, AFPlevel, pathological grade, staging, carcino-embolus and recurrence. The sensitivity ofAFP detection (≥400ug/L) in36HCC patients was44.4%，and The sensitivity of AFP detection(≥20ug/L) was69.4%. while the sensitivity of FHIT and RASSF1A gene promoterhypermethylation detection in36HCC patients is72.2％. In20patients whose AFP<400ug/L, the frequency of hypermethylation of the two genes together was80%,When AFP<20ug/L, the frequency of hypermethylation of the two genes together was54.5%. Conclusion We observed a statistically significant concordance betweenplasma and tissue methylation profiles. The methylation status in plasma and tumortissue had no correlation to patients’ clinicopathological features. Combined genespromoter methylation detection in plasma is superior to APF in HCC diagnosis.