Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

<h4>Background</h4>Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to te...

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Autores principales:	Aileen Marshall, Margus Lukk, Claudia Kutter, Susan Davies, Graeme Alexander, Duncan T Odom
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4710eeb163bc49b89febcd57a8de9f8a
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spelling	oai:doaj.org-article:4710eeb163bc49b89febcd57a8de9f8a2021-11-18T07:53:06ZGlobal gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.1932-620310.1371/journal.pone.0059459https://doaj.org/article/4710eeb163bc49b89febcd57a8de9f8a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527199/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets.<h4>Methodology and principal findings</h4>Global gene expression profiling was performed for 4 normal (control) livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH) undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV) cirrhosis, HCV-related HCC (HCV-HCC), hepatitis B virus (HBV) cirrhosis and HBV-related HCC (HBV-HCC). Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC) were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1) mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072) and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.<h4>Conclusion</h4>HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be evaluated in future studies.Aileen MarshallMargus LukkClaudia KutterSusan DaviesGraeme AlexanderDuncan T OdomPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59459 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aileen Marshall Margus Lukk Claudia Kutter Susan Davies Graeme Alexander Duncan T Odom Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
description	<h4>Background</h4>Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets.<h4>Methodology and principal findings</h4>Global gene expression profiling was performed for 4 normal (control) livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH) undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV) cirrhosis, HCV-related HCC (HCV-HCC), hepatitis B virus (HBV) cirrhosis and HBV-related HCC (HBV-HCC). Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC) were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1) mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072) and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.<h4>Conclusion</h4>HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be evaluated in future studies.
format	article
author	Aileen Marshall Margus Lukk Claudia Kutter Susan Davies Graeme Alexander Duncan T Odom
author_facet	Aileen Marshall Margus Lukk Claudia Kutter Susan Davies Graeme Alexander Duncan T Odom
author_sort	Aileen Marshall
title	Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
title_short	Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
title_full	Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
title_fullStr	Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
title_full_unstemmed	Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.
title_sort	global gene expression profiling reveals spink1 as a potential hepatocellular carcinoma marker.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4710eeb163bc49b89febcd57a8de9f8a
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Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

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