Personalized Medicine and Imaging 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 correlatedwith the treatment outcomes. The expression TGF-b1and the sensitivity to sorafenibwere examined inHCCcell lines. Results: Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (þ), and 11 (12%) were antihepatitis C virus (þ). 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 1⁄4 0.022) and overall survival (median 5.6 vs. 11.6 months; P 1⁄4 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 1⁄4 29, P 1⁄4 0.010). In preclinical models of HCC, higher TGF-b1 expression levels were associated with poorer sensitivity to sorafenib. Conclusion: 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; 1–7. 2015 AACR.