Gut Liver.  2018 May;12(3):306-315. 10.5009/gnl17277.

Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays

Affiliations
  • 1Department of Internal Medicine, Oncology and Rehabilitation, Paracelsus Hospital, Scheidegg, Germany. dr.holger.hass@paracelsus-kliniken.de
  • 2Department of Pathology, University of Tübingen, Tübingen, Germany.
  • 3Department of Gastroenterology, Oncology, Rheumatology, University of Würzburg, Würzburg, Germany.
  • 4Matrigene GmbH Company, Reutlingen, Germany.

Abstract

BACKGROUND/AIMS
The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed.
METHODS
To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (AffymetrixU133A) were used. Overexpressed genes were checked for their potential use as new markers for discrimination and their expression values were validated by reverse transcription polymerase chain reaction and immunohistochemistry analyses.
RESULTS
695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p < 0.05, fold change >2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and non-malignant liver tissues was established. A panel of 12 genes (e.g., HSP90β, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers.
CONCLUSIONS
A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.

Keyword

Cholangiocarcinoma; Carcinoma, hepatocellular; Oligonucleotide arrays; Gene expression analysis; Immunohistochemistry

MeSH Terms

Carcinoma, Hepatocellular
Cholangiocarcinoma
Discrimination (Psychology)*
Gene Expression*
Immunohistochemistry
Learning
Liver Neoplasms
Liver*
Methods
Oligonucleotide Array Sequence Analysis*
Polymerase Chain Reaction
Reverse Transcription
Transcriptome
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