Abstract 2865: High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: TGF-β (Transforming growth factor β) signaling pathway plays a significant role in mediating progression, metastasis, and immune evasion of human malignancies. Previous studies have found that serum TGF-β1 levels were elevated in patients with hepatocellular carcinoma (HCC) compared to patients with chronic hepatitis or cirrhosis. However, the prognostic role of serum TGF-β1 levels in patients with advanced HCC is currently unknown. Patients and Methods: We enrolled patients who had received sorafenib or sorafenib-based combination therapy for advanced HCC, defined as metastatic or locally advanced diseases not amenable to loco-regional therapies, at National Taiwan University Hospital, Taipei, Taiwan, between 2007 and 2012. The baseline blood samples were collected before sorafenib treatment with the consent of the patients. Serum TGF-β1 levels were measured by Human TGF-β1 Instant ELISA (eBioscience, Vienna, Austria), and were correlated with disease control rate (DCR), progression- free survival (PFS), and overall survival (OS) of the patients. Results: The study enrolled 91 patients (M:F=82:9), with a median age of 56.9 years. Sixty-nine patients (75.8 %) had chronic hepatitis B virus (HBV) infection, 18 (19.7%) had chronic hepatitis C infection, 82 (90.1%) had Barcelona Clinic Liver Cancer stage C disease, 81(89.0%) had either extrahepatic metastasis or macrovascular invasion, and 88 (96.7%) had Eastern Cooperative Oncology Group performance status of ≤ 1. All patients had Child-Puch class A liver function reserve. Patients with high baseline serum TGF-β1 levels (higher than the median level of the whole patient cohort), compared to patients with low serum TGF-β1 levels, had significantly shorter PFS (median, 2.54 vs. 4.27 months, p = 0.022) and OS (median, 5.57 vs. 11.6 months, p = 0.029). The DCRs for patients with high and low TGF-β1 were not statistically different (54.3 % vs. 62.2%, p = 0.4463). High baseline TGF-β1 levels tended to associate with high serum alpha-fetal protein (AFP) levels and high Cancer of the Liver Italian Program (CLIP) scores, although not reaching statistical significance. Conclusions: High baseline serum TGF-β1 levels were associated with poor PFS and OS in patients with advanced HCC. (This study was supported by grants NRPB-100CAP1020-2, NSC101-2314-B-002-141 & NSC102-2314-B-002 -120). Citation Format: Tzu-Hsuan Lin, Yu-Yun Shao, Soa-Yu Chan, Chung-Yi Huang, Ann-Lii Cheng, Chih-Hung Hsu. High serum transforming growth factor β1 levels associated with poor survivals in patients with advanced hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2865. doi:10.1158/1538-7445.AM2014-2865