Utilizing-score to identify oncogenic pathways of cholangiocarcinoma

Tzu Hung Hsiao, Hung I Harry Chen, Jo Yang Lu, Pei Ying Lin, Charles Keller, Sarah A Comerford, Gail E. Tomlinson, Yidong Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Extracting maximal information from gene signature sets (GSSs) via microarray-based transcriptional profiling involves assigning function to up and down regulated genes. Here we present a novel sample scoring method called Signature-score (S-score) which can be used to quantify the expression pattern of tumor samples from previously identified gene signature sets. A simulation result demonstrated an improved accuracy and robustness by S-score method comparing with other scoring methods. By applying the S-score method to cholangiocarcinoma (CAC), an aggressive hepatic cancer that arises from bile ducts cells, we identified enriched oncogenic pathways in two large CAC data sets. Thirteen pathways were enriched in CAC compared with normal liver and bile duct. Moreover, using S-score, we were able to dissect correlations between CAC-associated oncogenic pathways and Gene Ontology function. Two major oncogenic clusters and associated functions were identified. Cluster 1, which included beta-catenin and Ras, showed a positive correlation with the cell cycle, while cluster 2, which included TGF-beta, cytokeratin 19 and EpCAM was inversely correlated with immune function. We also used S-score to identify pathways that are differentially expressed in CAC and hepatocellular carcinoma (HCC), the more common subtype of liver cancer. Our results demonstrate the utility and effectiveness of -score in assigning functional roles to tumor-associated gene signature sets and in identifying potential therapeutic targets for specific liver cancer subtypes.

Original languageEnglish (US)
Pages (from-to)6-17
Number of pages12
JournalTranslational Cancer Research
Volume2
Issue number1
DOIs
StatePublished - Feb 1 2013

Fingerprint

Cholangiocarcinoma
Liver Neoplasms
Genes
Research Design
Bile Duct Neoplasms
Keratin-19
Gene Ontology
beta Catenin
Bile Ducts
Transforming Growth Factor beta
Hepatocellular Carcinoma
Neoplasms
Cell Cycle
Liver

Keywords

  • Gene signature set
  • Pathway analysis
  • S-score method
  • Tumor classification

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Utilizing-score to identify oncogenic pathways of cholangiocarcinoma. / Hsiao, Tzu Hung; Chen, Hung I Harry; Lu, Jo Yang; Lin, Pei Ying; Keller, Charles; Comerford, Sarah A; Tomlinson, Gail E.; Chen, Yidong.

In: Translational Cancer Research, Vol. 2, No. 1, 01.02.2013, p. 6-17.

Research output: Contribution to journalArticle

Hsiao, TH, Chen, HIH, Lu, JY, Lin, PY, Keller, C, Comerford, SA, Tomlinson, GE & Chen, Y 2013, 'Utilizing-score to identify oncogenic pathways of cholangiocarcinoma', Translational Cancer Research, vol. 2, no. 1, pp. 6-17. https://doi.org/10.3978/j.issn.2218-676X.2012.12.04
Hsiao, Tzu Hung ; Chen, Hung I Harry ; Lu, Jo Yang ; Lin, Pei Ying ; Keller, Charles ; Comerford, Sarah A ; Tomlinson, Gail E. ; Chen, Yidong. / Utilizing-score to identify oncogenic pathways of cholangiocarcinoma. In: Translational Cancer Research. 2013 ; Vol. 2, No. 1. pp. 6-17.
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