ABSTRACT
The transforming growth factor [TGF]-beta 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-beta1 level and TGF-beta1 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-beta1 gene expression in peripheral blood was quantitated using real-time polymerase chain reaction [PCR], while serum TGF-beta1 was analysed using enzyme-linked immunosorbent assay [ELISA]. TGF-beta1 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-beta1 gene expression showed significant positive correlation with serum TGF-beta1 [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-beta1 gene expression in comparison with AFP. The area under the curve for TGF-beta1 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-beta1 gene expression were 65% and 75%, respectively, at a cutoff value of 0.462 fold change. TGF-beta1 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-beta1 gene expression in the pathogenesis of HCC