Gene expression analysis in serial liver fine needle aspirates

• Published in: Journal of viral hepatitis 2015-01, Vol.22 (1), p.64-76
• Main Authors: 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., Talal, A. H.
• Format: Article
• Language: English
• Subjects: Adult; Animals; Biopsy, Fine-Needle; Dogs; Female; Gene expression; Gene Expression Profiling - methods; Hepatitis; Hepatitis C, Chronic - pathology; Humans; Liver; Liver - pathology; liver sampling; Male; microarray; Microarray Analysis; Middle Aged; nucleic acid analysis; Real-Time Polymerase Chain Reaction; RNA; RNA amplification
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1111/jvh.12213

Summary 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