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Meta-analysis of gene expression profiles identifies differential biomarkers for hepatocellular carcinoma and cholangiocarcinoma

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Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the members of hepatobiliary diseases. Both types of cancer often exert high levels of similarity in terms of phenotypic characteristics, thus leading to difficulties in HCC and CCA differential diagnoses. In this study, a transcriptome meta-analysis was performed on HCC and CCA microarray data to identify differential transcriptome networks and potential biomarkers for HCC and CCA. Raw data from nine gene expression profiling datasets, consisting of 1,185 samples in total, were methodologically compiled and analyzed. To evaluate differentially expressed (DE) genes in HCC and CCA, the levels of gene expression were compared between cancer and its normal counterparts (i.e., HCC versus normal liver and CCA versus normal bile duct) using t test (P < 0.05) and k-fold validation. A total of 226 DE genes were specific to HCC, 249 DE genes specific to CCA, and 41 DE genes in both HCC and CCA. Gene ontology and pathway enrichment analyses revealed different patterns between functional transcriptome networks of HCC and CCA. Cell cycle and glycolysis/gluconeogenesis pathways were exclusively dysregulated in HCC whereas complement and coagulation cascades as well as glycine, serine, and threonine metabolism were prodominantly differentially expressed in CCA. Our meta-analysis revealed distinct dysregulation in transcriptome networks between HCC and CCA. Certain genes in these networks were discussed in the context of HCC and CCA transition, unique characteristics of HCC and CCA, and their potentials as HCC and CCA differential biomarkers.

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Abbreviations

20-HETE :

20-Epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid

-OH-E1 :

4-Hydroxyestrone

CCA :

Cholangiocarcinoma

DE :

Differentially expressed

EMT :

Epithelial-mesenchymal transition process

GO :

Gene ontology

HCC :

Hepatocellular carcinoma

HPA :

Human protein atlas project

KEGG :

Kyoto encyclopedia of genes and genomes

NL :

Normal liver

NB :

Normal bile duct

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Acknowledgments

This work is supported by Medical Research Council (MRC) through UK-Thailand Research Collaborations (Newton Fund), the Thailand Research Fund (grant no. DBG5980006), and Mahidol University to TJ. SL is a recipient of the Development and Promotion of Science and Technology Talented Project (DPST) scholarship. JT is a recipient of the Science Achievement Scholarship of Thailand (SAST).

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  1. Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Somsak Likhitrattanapisal

  2. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Jaitip Tipanee & Tavan Janvilisri

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  1. Somsak Likhitrattanapisal
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  3. Tavan Janvilisri
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Correspondence to Tavan Janvilisri.

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Table S1

A list of differentially expressed genes in hepatocellular carcinoma compared to normal liver. (DOCX 29 kb)

Table S2

A list of differentially expressed genes in cholangiocarcinoma compared to normal bile duct. (DOCX 34 kb)

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Likhitrattanapisal, S., Tipanee, J. & Janvilisri, T. Meta-analysis of gene expression profiles identifies differential biomarkers for hepatocellular carcinoma and cholangiocarcinoma. Tumor Biol. 37, 12755–12766 (2016). https://doi.org/10.1007/s13277-016-5186-8

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