Kazuhiko Masuda1, Atsushi Ono2,3,4,5, Hiroshi Aikata6,7, Tomokazu Kawaoka6,7, C Nelson Hayes6,7,8, Yuji Teraoka6,7, Kana Daijo6,7, Yuki Nakamura-Inagaki6,7, Kei Morio6,7, Hatsue Fujino6,7, Hiromi Kan6,7, Takuro Uchida6,7, Keiichi Masaki6,7, Tomoki Kobayashi6,7, Takashi Nakahara6,7, Grace Naswa Makokha6,7, Yizhou Zhang6,7, Yuko Nagaoki6,7, Daiki Miki7,8, Masataka Tsuge6,7, Akira Hiramatsu6,7, Michio Imamura6,7, Hiromi Abe-Chayama6,7,8, Yoshiiku Kawakami6,7, Hidenori Ochi6,7,8, Kazuaki Chayama6,7,8. 1. Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. masu6743@hiroshima-u.ac.jp. 2. Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. atsushi-o@hiroshima-u.ac.jp. 3. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. atsushi-o@hiroshima-u.ac.jp. 4. Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. atsushi-o@hiroshima-u.ac.jp. 5. Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, Box 1123, New York, NY, 10029, USA. atsushi-o@hiroshima-u.ac.jp. 6. Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 7. Liver Research Project Center, Hiroshima University, Hiroshima, Japan. 8. Laboratory for Digestive Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
Abstract
BACKGROUND: Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis. METHODS: Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis. RESULTS: Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P < 0.0001) as independent predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P < 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks. CONCLUSIONS: These results suggest that serum HMGB1 at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or HAIC.
BACKGROUND: Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis. METHODS: Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis. RESULTS: Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P < 0.0001) as independent predictors of poor overall survival in sorafenib treatment. High HMGB1 at 4 weeks (P = 0.025), vascular invasion to the hepatic vein (Vv) (P = 0.009), mRECIST (P < 0.0001) and Child-Pugh B (P = 0.004) were identified as independent predictors of poor overall survival in HAIC treatment. The concentrations of HMGB1 at baseline and 4 weeks were not correlated with conventional tumor markers and progressive disease assessed by mRECIST at 8 weeks. CONCLUSIONS: These results suggest that serum HMGB1 at 4 weeks after the start of treatment might be a useful biomarker with added value to the conventional tumor marker and radiologic responses to predict poor overall survival in patients with advanced HCC treated with sorafenib or HAIC.
Entities:
Keywords:
Biomarker; HCC; Hepatic arterial infusion chemotherapy; High mobility group box 1; Liver cancer; Sorafenib
Authors: Bernardo L Rapoport; Helen C Steel; Annette J Theron; Liezl Heyman; Teresa Smit; Yastira Ramdas; Ronald Anderson Journal: Cells Date: 2020-07-10 Impact factor: 6.600