|Title:||High Serum Transforming Growth Factor-beta 1 Levels Predict Outcome in Hepatocellular Carcinoma Patients Treated with Sorafenib||Authors:||Lin, Tzu-Hsuan
|Issue Date:||2015||Journal Volume:||21||Journal Issue:||16||Start page/Pages:||3678-3684||Source:||Clin. Cancer Res.||Abstract:||
Background: The TGF-beta signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-beta 1 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-beta 1 levels were measured and correlated with the treatment outcomes. The expression TGF-beta 1 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-beta 1 levels (median 13.7 ng/mL; range, 3.0-41.8) were associated with high alpha-fetoprotein levels, but not with age, gender, or disease stage. Patients with high pretreatment serum TGF-beta 1 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-beta 1 levels. Compared with pretreatment levels, the serum TGF-beta 1 levels were significantly increased at disease progression (n = 29, P = 0.010). In preclinical models of HCC, higher TGF-beta 1 expression levels were associated with poorer sensitivity to sorafenib. ;Conclusions: High pretreatment serum TGF-beta 1 levels were associated with poor prognoses, and increased serum TGF-beta 1 levels were associated with the disease progression of advanced HCC patients. TGF-beta pathway may be explored as a therapeutic target for advanced HCC. (C)2015 AACR.
|Appears in Collections:||腫瘤醫學研究所|
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