Clinical impact of plasma TGF-beta1 and circulating TGF-beta1 mRNA in diagnosis of hepatocellular carcinoma.

ABSTRACT

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of cell growth and differentiation, angiogenesis, extracellular matrix formation, immunosuppression and cancer development. In this study, we investigated the levels of TGF-beta1 and TGF-beta1 mRNA expression, their relationship with HBV replication, and their diagnostic value for hepatocellular carcinoma (HCC). METHODS: Total RNAs were extracted from HCC samples and matched non-tumor tissues, and from peripheral blood mononuclear cells in HCC patients. TGF-beta1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-beta1 expression was assessed by immunohistochemistry. The clinical characteristics were analyzed between TGF-beta1 and HBV replication. The diagnostic value of circulating TGF-beta1 and TGF-beta1 mRNA levels were investigated in HCC patients. RESULTS: The incidence of hepatic TGF-beta1 expression was 83.3% in HCC samples, 43.3% in the surrounding tissues, 94.7% in the HBV DNA-positive group, and 63.6% in the HBV DNA-negative group. Liver TGF-beta1 expression was associated with the degree of HCC differentiation and the status of HBV replication, but not with the size or number of tumors. Circulating TGF-beta1 level and incidence of TGF-beta1 mRNA were significantly higher in the HCC group than in any group of patients with benign liver disease, with a higher sensitivity of 89.5% and a specificity of 94.0% for HCC diagnosis when circulating TGF-beta1 levels were >1.2 microg/L. No significant correlation was found between TGF-beta1 expression and AFP level or tumor size. Combining TGF-beta1 level and serum AFP raised the detection rate to 97.4%. CONCLUSIONS: Abnormal expression of hepatic TGF-beta1 is associated with the degree of HCC differentiation and HBV replication. Both circulating TGF-beta1 and TGF-beta1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.