Yin-Hsun Feng1,2, Chao-Ling Tung3, Yu-Chu Su4,5, Chao-Jung Tsao6, Ting-Feng Wu7. 1. Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C. yinhsun.feng@gmail.com wutingfe@stust.edu.tw. 2. Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan, R.O.C. 3. Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C. 4. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C. 5. Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C. 6. Department of Hematology and Oncology, Chi-Mei Medical Center, Liouying Campus, Tainan, Taiwan, R.O.C. 7. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan, R.O.C. yinhsun.feng@gmail.com wutingfe@stust.edu.tw.
Abstract
BACKGROUND/AIM: The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been reported. MATERIALS AND METHODS: We exploited two-dimensional gel electrophoresis coupled with mass spectrometry to find de-regulated proteins by using conditioning of a sorafenib-resistant HCC cell line, Huh7. Tumor samples from 60 patients with HCC treated with sorafenib were analyzed and correlated with survival outcome. RESULTS: Comparative proteomics indicated three proteins including, 78 kDa glucose related protein (GRP78), 14-3-3ε, and heat shock protein 90β (HSP90β). The three proteins were over-expressed in sorafenib-resistant Huh7 cells. In HCC tumor samples from patients treated with sorafenib, 73% of tumor samples had a high expression of GRP78, 18% had high 14-3-3ε expression and 85% had high HSP90β expression. Among these, GRP78 was associated with the shortest progression-free survival of HCC patients treated with sorafenib. CONCLUSION: GRP78 can be a predictive biomarker in HCC patients treated with sorafenib. Strategies designed to inhibit the GRP78-related pathway may overcome sorafenib resistance. Copyright
BACKGROUND/AIM: The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been reported. MATERIALS AND METHODS: We exploited two-dimensional gel electrophoresis coupled with mass spectrometry to find de-regulated proteins by using conditioning of a sorafenib-resistant HCC cell line, Huh7. Tumor samples from 60 patients with HCC treated with sorafenib were analyzed and correlated with survival outcome. RESULTS: Comparative proteomics indicated three proteins including, 78 kDa glucose related protein (GRP78), 14-3-3ε, and heat shock protein 90β (HSP90β). The three proteins were over-expressed in sorafenib-resistant Huh7 cells. In HCC tumor samples from patients treated with sorafenib, 73% of tumor samples had a high expression of GRP78, 18% had high 14-3-3ε expression and 85% had high HSP90β expression. Among these, GRP78 was associated with the shortest progression-free survival of HCC patients treated with sorafenib. CONCLUSION:GRP78 can be a predictive biomarker in HCC patients treated with sorafenib. Strategies designed to inhibit the GRP78-related pathway may overcome sorafenib resistance. Copyright
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Elizabeth A Kuczynski; Melissa Yin; Avinoam Bar-Zion; Christina R Lee; Henriett Butz; Shan Man; Frances Daley; Peter B Vermeulen; George M Yousef; F Stuart Foster; Andrew R Reynolds; Robert S Kerbel Journal: J Natl Cancer Inst Date: 2016-04-08 Impact factor: 13.506
Authors: Chi Wai Yip; Ching Yan Lam; Terence C W Poon; Tan To Cheung; Phyllis F Y Cheung; Sze Wai Fung; Xiao Qi Wang; Idy C Y Leung; Linda W C Ng; Chung Mau Lo; George S W Tsao; Siu Tim Cheung Journal: BMC Cancer Date: 2017-06-10 Impact factor: 4.430