Yu-Yun Shao1,2,3, Pai-Sheng Chen4, Liang-In Lin5, Bin-Shyun Lee1, Andrew Ling6, Ann-Lii Cheng1,2,3,7, Chiun Hsu1,2,3, Da-Liang Ou8,9. 1. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City, 10055, Taiwan. 2. Department of Oncology, National Taiwan University Hospital, Taipei City, 10048, Taiwan. 3. National Taiwan University Cancer Center, Taipei City, 10672, Taiwan. 4. Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan City, 70101, Taiwan. 5. Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei City, 10048, Taiwan. 6. Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA. 7. Department of Internal Medicine, National Taiwan University Hospital, Taipei City, 10048, Taiwan. 8. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City, 10055, Taiwan. dlou@ntu.edu.tw. 9. YongLin Institute of Health, National Taiwan University, Taipei City, 10672, Taiwan. dlou@ntu.edu.tw.
Abstract
BACKGROUND: Sorafenib is one of the standard first-line therapies for advanced hepatocellular carcinoma (HCC). Unfortunately, there are currently no appropriate biomarkers to predict the clinical efficacy of sorafenib in HCC patients. MicroRNAs (miRNAs) have been studied for their biological functions and clinical applications in human cancers. METHODS: In this study, we found that miR-10b-3p expression was suppressed in sorafenib-resistant HCC cell lines through miRNA microarray analysis. RESULTS: Sorafenib-induced apoptosis in HCC cells was significantly enhanced by miR-10b-3p overexpression and partially abrogated by miR-10b-3p depletion. Among 45 patients who received sorafenib for advanced HCC, those with high miR-10b-3p levels, compared to those with low levels, exhibited significantly longer overall survival (OS) (median, 13.9 vs. 3.5 months, p = 0.021), suggesting that high serum miR-10b-3p level in patients treated with sorafenib for advanced HCC serves as a biomarker for predicting sorafenib efficacy. Furthermore, we confirmed that cyclin E1, a known promoter of sorafenib resistance reported by our previous study, is the downstream target for miR-10b-3p in HCC cells. CONCLUSIONS: This study not only identified the molecular target for miR-10b-3p, but also provided evidence that circulating miR-10b-3p may be used as a biomarker for predicting sorafenib sensitivity in patients with HCC.
BACKGROUND: Sorafenib is one of the standard first-line therapies for advanced hepatocellular carcinoma (HCC). Unfortunately, there are currently no appropriate biomarkers to predict the clinical efficacy of sorafenib in HCC patients. MicroRNAs (miRNAs) have been studied for their biological functions and clinical applications in human cancers. METHODS: In this study, we found that miR-10b-3p expression was suppressed in sorafenib-resistant HCC cell lines through miRNA microarray analysis. RESULTS: Sorafenib-induced apoptosis in HCC cells was significantly enhanced by miR-10b-3p overexpression and partially abrogated by miR-10b-3p depletion. Among 45 patients who received sorafenib for advanced HCC, those with high miR-10b-3p levels, compared to those with low levels, exhibited significantly longer overall survival (OS) (median, 13.9 vs. 3.5 months, p = 0.021), suggesting that high serum miR-10b-3p level in patients treated with sorafenib for advanced HCC serves as a biomarker for predicting sorafenib efficacy. Furthermore, we confirmed that cyclin E1, a known promoter of sorafenib resistance reported by our previous study, is the downstream target for miR-10b-3p in HCC cells. CONCLUSIONS: This study not only identified the molecular target for miR-10b-3p, but also provided evidence that circulating miR-10b-3p may be used as a biomarker for predicting sorafenib sensitivity in patients with HCC.
Authors: Jorge A Marrero; Laura M Kulik; Claude B Sirlin; Andrew X Zhu; Richard S Finn; Michael M Abecassis; Lewis R Roberts; Julie K Heimbach Journal: Hepatology Date: 2018-08 Impact factor: 17.425
Authors: Paloma Del C Monroig-Bosque; Maitri Y Shah; Xiao Fu; Enrique Fuentes-Mattei; Hui Ling; Cristina Ivan; Nazila Nouraee; Beibei Huang; Lu Chen; Valentina Pileczki; Roxana S Redis; Eun-Jung Jung; Xinna Zhang; Michael Lehrer; Rahul Nagvekar; Ana Carolina P Mafra; Maria Del Mar Monroig-Bosque; Alexandra Irimie; Carlos Rivera; Calin Dan Dumitru; Ioana Berindan-Neagoe; Edward P Nikonowicz; Shuxing Zhang; George A Calin Journal: Sci Rep Date: 2018-08-30 Impact factor: 4.379