Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib.

Abstract

Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the median overall survival (OS) benefit is only ~3 months, and sufficient biomarkers predicting treatment response are not available. The aim of the present study was to evaluate miRNA expression patterns from HCC tissue biopsies as potential biomarkers in patients under sorafenib treatment. Nineteen patients with advanced HCC treated with sorafenib were included. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsies. miRNA expression profiling of 818 mature miRNAs was performed using GeneChip® miRNA Array 2.0 (Affymetrix). Global miRNA patterns were assessed using unsupervised hierarchical clustering analysis (UCA), and specific miRNAs with correlation with disease control rate (DCR) or good OS were evaluated by pairwise supervised analyses. UCA divided the patients into three distinct groups by their miRNA expression patterns. However, DCR or OS did not correlate with these sub-groups. We have identified several miRNAs that correlated with either DCR or OS (P<0.05). However, with correction for multiple testing, these results did not reach statistical significance in this small cohort. Global miRNA analysis from very low input RNA deriving from liver biopsies showed distinctive clustering of molecular sub-groups in patients with intermediate and advanced HCC. Clinical response including OS under sorafenib did not correlate with global miRNA expression patterns, but we have identified candidate miRNAs for the prediction of DCR and OS to be evaluated in prospective studies and larger patient cohorts.

• Authors: Jan Peveling-Oberhag, Claudia Döring, Sylvia Hartmann, Natalie Filmann, Angelika Mertens, Albrecht Piiper, Eva Herrmann, Martin-Leo Hansmann, Stefan Zeuzem, Jörg Trojan, Martin-Walter Welker
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 128 Issue 1 Pg. 29-37 (Jan 2015) ISSN: 1470-8736 [Electronic] England
• PMID: 24959956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Genetic Markers
• MicroRNAs
• Phenylurea Compounds
• Niacinamide
• Sorafenib

Topics

• Antineoplastic Agents (therapeutic use)
• Biopsy, Fine-Needle
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Feasibility Studies
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Genetic Markers (genetics)
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Male
• MicroRNAs (metabolism)
• Middle Aged
• Niacinamide (analogs & derivatives, therapeutic use)
• Oligonucleotide Array Sequence Analysis (methods)
• Phenylurea Compounds (therapeutic use)
• Real-Time Polymerase Chain Reaction
• Retrognathia
• Sorafenib
• Treatment Outcome