MicroRNA-425-3p predicts response to sorafenib therapy in patients with hepatocellular carcinoma
Article first published online: 20 JUL 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 35, Issue 3, pages 1077–1086, March 2015
How to Cite
Liver Int. 2015; 35: 1077–1086
- Issue published online: 11 FEB 2015
- Article first published online: 20 JUL 2014
- Accepted manuscript online: 10 JUL 2014 09:57AM EST
- Manuscript Accepted: 5 JUL 2014
- Manuscript Received: 19 FEB 2014
- Fondazione Berlucchi
- Fondazione Cariplo. Grant Number: 2010-0846
- AIRC. Grant Number: 2010-10247
- hepatocellular carcinoma;
Background & Aims
Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients.
We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set). Formalin-fixed paraffin-embedded tumour and cirrhotic liver biopsies were used for RNA extraction and miRNAs profiling with TaqMan Arrays technology. Statistical analyses were used to correlate miRNA levels with clinical outcome, including time to progression (TTP), progression free (PFS), and overall survival. Cell viability and cell motility of HuH-7 or HepG2 HCC cells were tested in vitro after transfection with specific miRNA precursor, inhibitor or controls and sorafenib treatment.
Six miRNAs were significantly associated with clinical variables in the training set and only miR-425-3p could be further validated. Higher levels of miR-425-3p were associated with longer TTP and PFS (P = 0.0008; HR = 0.4; 95% CI = 0.2–0.7 and P = 0.007; HR = 0.5; 95% CI = 0.3–0.9 respectively). Multivariate analysis confirmed the predictive significance of miR-425-3p. Furthermore, an association between increased miR-425-3p, cell death and reduced cell motility was defined in vitro in HCC cell lines treated with sorafenib.
Assessment of miR-425-3p levels in liver biopsies could help in stratifying patients with advanced HCC for sorafenib treatment. These promising results need to be confirmed in a large prospective study.