These authors contributed equally to this work.
Gene expression analysis in serial liver fine needle aspirates
Article first published online: 29 JAN 2014
© 2014 John Wiley & Sons Ltd
Journal of Viral Hepatitis
Volume 22, Issue 1, pages 64–76, January 2015
How to Cite
Lejnine, S., Marton, M. J., Wang, I.-M., Howell, B. J., Webber, A. L., Maxwell, J. W., Shire, N., Malkov, V., Lunceford, J., Zeremski, M., Sun, A., Ruddy, M. and Talal, A. H. (2015), Gene expression analysis in serial liver fine needle aspirates. Journal of Viral Hepatitis, 22: 64–76. doi: 10.1111/jvh.12213
- Issue published online: 23 DEC 2014
- Article first published online: 29 JAN 2014
- Manuscript Accepted: 8 OCT 2013
- Manuscript Received: 9 SEP 2013
- Merck and Co.
- Clinical and Translational Science Center. Grant Number: ULI RR024996
- liver sampling;
- nucleic acid analysis;
- RNA ;
- RNA amplification
No method with low morbidity presently exists for obtaining serial hepatic gene expression measurements in humans. While hepatic fine needle aspiration (FNA) has lower morbidity than core needle biopsy, applicability is limited due to blood contamination, which confounds quantification of gene expression changes. The aim of this study was to validate FNA for assessment of hepatic gene expression. Liver needle biopsies and FNA procedures were simultaneously performed on 17 patients with chronic hepatitis C virus infection with an additional FNA procedure 1 week later. Nine patients had mild/moderate fibrosis and eight advanced fibrosis. Gene expression profiling was performed using Affymetrix microarrays and TaqMan qPCR; pathway analysis was performed using Ingenuity. We developed a novel strategy that applies liver-enriched normalization genes to determine the percentage of liver in the FNA sample, which enables accurate gene expression measurements overcoming biases derived from blood contamination. We obtained almost identical gene expression results (ρ = 0.99, P < 0.0001) comparing needle biopsy and FNA samples for 21 preselected genes. Gene expression results were also validated in dogs. These data suggest that liver FNA is a reliable method for serial hepatic tissue sampling with potential utility for a variety of preclinical and clinical applications.