Transforming growth factor-β1 gene expression in hepatocellular carcinoma: a preliminary report.

Background And Study Aims: The transforming growth factor (TGF)-β signalling pathway plays a dual role in hepatocarcinogenesis. It has been recognised for its role as a tumour suppressor as well as a tumour promoter depending on the cellular context. The aim of this study was to investigate the clinical significance of serum TGF-β1 level and TGF-β1 messenger RNA (mRNA) in the peripheral blood of liver cirrhosis and hepatocellular carcinoma (HCC) patients as noninvasive biomarkers in diagnosing HCC.

Patients And Methods: Twenty patients were allocated to each of the liver cirrhosis and HCC groups, in addition to 20 healthy volunteers. TGF-β1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction (PCR), while serum TGF-β1 was analysed using enzyme-linked immunosorbent assay (ELISA).

Results: TGF-β1 gene expression was significantly lower in HCC patients (median 0.401 (0.241-0.699) fold change) than in liver cirrhosis patients (median 0.595 (0.464-0.816)) (p=0.042) and normal controls (median 1.00 (0.706-1.426) fold change) (p=0.001). TGF-β1 gene expression showed significant positive correlation with serum TGF-β1 (r=0.272, p=0.036) and significant negative correlation with alpha-fetoprotein (AFP) (r=-0.528, p=0.001). Receiver operating characteristic (ROC) analysis was conducted for TGF-β1 gene expression in comparison with AFP. The area under the curve for TGF-β1 gene expression was 0.688 (95% CI=0.517-0.858) (p=0.042) and AFP was 0.869 (95% CI=0.761-0.976) (p=0.001). The sensitivity and specificity of TGF-β1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change.

Conclusion: TGF-β1 gene expression in the peripheral blood may be used as a molecular marker for the diagnosis of HCC. Additional studies on a large-scale population are necessary to gain greater insight into the impact of TGF-β1 gene expression in the pathogenesis of HCC.