LAUSR

Background: Recently, the new effect of branched-chain amino acid (BCAA) on Osteopontin (OPN), which correlates with cancer progression, has been reported. The aim of this study was that preoperative administration of BCAA could improve prognosis via degradation of OPN expression in hepatocellular carcinoma (HCC). Methods: Human hepatocellular carcinoma cell lines were treated with BCAA (2nM), and investigated OPN expression, cell proliferation and invasion in vitro. Next, patients undergoing elective liver resections for HCC (n=72) were randomized to receive or not receive preoperative oral supplementation with BCAA. OPN protein levels in HCC patients were examined using immunohistochemistry and compared with the clinicopathologic features of the tumors. Results: Experimentally, the expression levels of OPN were significantly decreased in HCC cells treated with BCAA. BCAA treatment significantly decreased cell invasion. In the clinical setting, OPN expression correlated with HBV or HCV infection (p = 0.03), venous invasion (p = 0.02) and liver fibrosis (p = 0.07). There was no difference in both DFS and OS between OPN-positive and OPN-negative group, and preoperative BCAA administration did not improve prognosis, either. For the patients without late recurrence, OPN-positive group showed significantly poor outcome in DFS (p = 0.047), and preoperative BCAA administration improved DFS (p = 0.062). Conclusions: OPN expression was associated with cancer cell invasion and intrahepatic metastasis. BCAA treatment suppressed HCC cell invasion and preoperative BCAA administration prevented early intrahepatic recurrence by decreasing the expression level of OPN in HCC. Citation Format: Yukihiko Hiroshima, Yasuhiro Yabushita, Yutaro Kikuchi, Daisuke Kawagushi, Takashi Murakami, Yasushi Ichikawa, Itaru Endo, Kuniya Tanaka. Preoperative supplementation of branched-chain amino acids suppresses Osteopontin expression in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4188.