title: MicroRNAs for the Prediction of Early Response to Sorafenib Treatment in Human Hepatocellular Carcinoma.
abstract: BACKGROUND
  Several studies suggest the role of circulating microRNAs (miRNAs) as biomarkers of hepatocellular carcinoma (HCC). However, the serum miRNA profile associated with the response to sorafenib remains to be elucidated. The aim of this study was to clarify the specific miRNAs in serum that could predict the early response of HCC to sorafenib treatment.
  
  
  CONCLUSIONS
  Analyzing the sera from 16 HCC patients, we selected five miRNAs that showed differences in serum levels between patients with and without tumor responses among 179 known secretory miRNAs by using locked nucleic acid probe-based quantitative PCR. Through further analysis using a validation cohort that included 53 HCC patients who underwent sorafenib treatment and 8 healthy control subjects, we found that miR-181a-5p and miR-339-5p showed significant differences in serum levels among patients with partial response (PR), stable disease (SD), and progressive disease (PD), where PR patients showed the highest and PD the lowest levels. We also analyzed the factors associated with disease control (DC; PR or SD) 3 months after the initiation of sorafenib treatment; patients with DC showed a significantly higher level of serum miR-181a-5p than non-DC patients or healthy control subjects (p = 0.0349 and 0.0180 for DC vs. non-DC and control vs. non-DC by Tukey-Kramer test, respectively). We further conducted multivariate analysis among HCC patients with Barcelona Clinic Liver Cancer stage C using extrahepatic metastasis, serum decarboxyprothrombin, and miR-181a-5p levels as covariables; serum miR-181a-5p was the only independent factor for achieving DC (p = 0.0092, odds ratio 0.139, and 95% confidence interval 0.011-0.658). In addition, miR-181a-5p level was also the only independent factor affecting overall survival (p = 0.0194, hazard ratio 0.267, and 95% confidence interval 0.070-0.818).
  
  
  CONCLUSIONS
  A high serum level of miR-181a-5p before treatment is associated with DC after the initiation of sorafenib.
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Arizumi
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ida
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
keywords: Biomarkers; Hepatocellular carcinoma; Molecular targeted therapy; Treatment; microRNA