Tumor Biology

, Volume 36, Issue 8, pp 5891–5899 | Cite as

Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis

  • Tong-Chun Xue
  • Bo-Heng Zhang
  • Sheng-Long Ye
  • Zheng-Gang Ren
Research Article


Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are common primary liver cancers worldwide. However, the survival and prognosis of ICC are much poorer than those of HCC, indicating the different molecular characteristics and mechanisms between ICC and HCC. To identify differentially expressed (DE) genes between ICC and HCC or combined hepatocellular-cholangiocarcinoma (CHC), we performed integrated analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets by MetaOmics. Three GEO datasets comprising 32 ICC biochips, 77 HCC biochips, and 34 CHC biochips were available for the data integration. We identified 7313 DE genes between ICC and HCC, including 3650 upregulated genes and 3663 downregulated genes. The S100 family members on chromosome 1q21 were extensively upregulated in ICC, and S100A11 had the greatest degree of upregulation in ICC. Based on the DE genes, combined gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed the enhanced pathways of local adhesion, ECM-receptor interaction, and regulation of action cytoskeleton, suggesting the enhanced communication between ICC and the microenvironment. Additionally, development-related genes and development-related pathways, including the Notch, Wnt, and TGF-β signaling pathways, were shown to be active prominently in ICC. Taken together, we identified the characteristically upregulated or downregulated DE genes and pathways in ICC compared with HCC or CHC. These DE genes and pathways supply new transcriptomics evidence for ICC and could help identify new therapeutic targets.


Microarray Hepatocellular carcinoma Cholangiocarcinoma Meta-analysis OMICS S100A11 



We thank Professor Andreas Heider (Translational Centre for Regenerative Medicine Leipzig, University of Leipzig, Germany) for help with virtualArray package usage and R software. This study was supported by The National Clinical Key Special Subject of China, The National Natural Science Foundation of China (81172275 and 21272565), and The National Basic Research Program of China (973 Program, 2009CB521700).

Conflicts of interest


Supplementary material

13277_2015_3261_MOESM1_ESM.xlsx (97 kb)
ESM 1 Overexpressed differentiated expressed genes in ICC compared with HCC (XLSX 96 kb)
13277_2015_3261_MOESM2_ESM.xlsx (95 kb)
ESM 2 Underexpressed differentiated expressed genes in ICC compared with HCC (XLSX 95 kb)
13277_2015_3261_MOESM3_ESM.xlsx (161 kb)
ESM 3 Total differentiated expressed genes in ICC compared with HCC by REM method (XLSX 160 kb)
13277_2015_3261_MOESM4_ESM.docx (20 kb)
ESM 4 Twenty genes overexpressed in ICC compared with CHC (DOCX 19 kb)
13277_2015_3261_MOESM5_ESM.tif (53 kb)
ESM 5 Gene ontology enrichment in ICC compared with HCC (TIFF 52 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Tong-Chun Xue
    • 1
    • 2
  • Bo-Heng Zhang
    • 1
    • 2
    • 3
  • Sheng-Long Ye
    • 1
    • 2
  • Zheng-Gang Ren
    • 1
    • 2
  1. 1.Liver Cancer Institute, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University)Ministry of EducationShanghaiPeople’s Republic of China
  3. 3.Department of Medical Statistics, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China

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