High Serum Transforming Growth Factor b1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib
Background: The TGF b signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF b1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC) Experimental Design: We selected patients who had received sorafenib containing regimens as first line therapy for advanced HCC between 2007 and 2012. Serum TGF b1 levels were measured and correlated with the treatment outcomes. The expression TGF b1 and the sensitivity to sorafenib were examined in HCC cell lines. Results:Ninety one patients were included; 62 (68% were hepatitis B virus surface antigen and 11 (12% were anti hepatitis C virus High median) pretreatment serum TGF b1 levels (median 13.7 ng/mL; range, 3.0 41.8) were associated with high a fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF b1 levels exhibited significantly shorter progression free survival (median, 2.5 vs. 4.3 months; P 0.022) and overall survival (median 5.6 vs. 11.6 months; P 0.029) than did patients with low serum TGF b1 levels. Compared with pretreatment levels, the serum TGF b1 levels were significantly increased at disease progression (n 29, P 0.010) In preclinical models of HCC, higher TGF b1 expression levels were associated with poorer sensitivity to sorafenib. Conclusions: High pretreatment serum TGF b1 levels were associated with poor prognoses, and increased serum TGF b1 levels were associated with the disease progression of advanced HCC patients. TGF b pathway may be explored as a therapeutic target for advanced HCC. Clin Cancer Res; 21(16) 3678 84. (c)2015 AACR.
Clinical Cancer Research