A Study Of The Prevention Value Between DNA Methylation In Plasma Associated With Prognosis And Blood Folate Levels In Hepatocellular Carcinoma And Esophageal Squamous Cell Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. In general, prognosis remains poor, thus identification of useful molecular prognostic markers is necessary. Aberrant promoter hypermethylation is an important mechanism leading to loss of gene function in tumors including HCC. Folate and methionine are dietary methyl group donors that may be hypothesized to influence DNA methylation. Low folate status or intake was suggested to decrease genomic methylation. Circulating folate concentration was associated with increased gene promoter hypermethylation. The hypermethylated subtype in tumors, called the CpG island methylator phenotype (CIMP) in which multiple genes are concurrently methylated, is a novel marker of tumor progression. Methylation of CpG islands in the promoters of many tumor suppressor genes effectively silences those genes. These epigenetic alterations may be important early events in carcinogenesis and may also be potential biomarkers for early detection. CIMP is an important mechanism in HCC development and may serve as a molecular marker of late-stage HCC with poor prognosis. CIMP status was analyzed using a methylation marker panel in tumor tissues and plasma with methylation-specific polymerase chain reaction and blood folate levels was assayed by using enzyme linked immunosorbent assay(ELISA). Epidemiological study was done in the ward. At the same time, the role of gene methylation related esophageal cancer in the Wnt signaling pathway was studied.The main results of the paper is as follows:(1)The frequencies of high-level methylation in HCC tissue and plasma were at least 15%. The methylation status of multiple genes in plasma may serve as a molecular marker of HCC with the early diagnosis.There is good concordance of DNA methylation in plasma and tumor in HCC.(2) CIMP associated with tumor not only in tumor tissue but also in plasma were significantly different in HCC with Gender,HBsAg,AFP and TNM stage and in nonneoplastic tissues and plasma of healthy controls. The metastatic rate and recurrence rate in CIMP+group were significantly higher than CIMP-group in plasma(p<0.05). In this study,Plasma DNA could be used as a reliable resource and replace tumor tissue for CIMP research. CIMP in plasma could serve as a molecular marker of late stage and poorly prognostic HCC.(3) Blood folate levels is associated with positive expression of CpG island methylation phenotype (CIMP) and CIMP+status and low blood folate levels were frequently be associated with tumor metastasis and recurrence.Increased folate levels in HCC may be prevent the further development of HCC.(4) SFRP-1, DKK-3 and RUNX-3 gene promoter methylation status in plasma can be individually and jointly predict esophageal cancer recurrence. The status of promoter hypermethylation of Wnt antagonists/inhibitors in plasma may serve as a non-invasive prognostic biomarker for ESCC.