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

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.

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).

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.

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.