Utilizing-score to identify oncogenic pathways of cholangiocarcinoma

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

研究成果: 雜誌貢獻文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)6-17
頁數12
期刊Translational Cancer Research
2
發行號1
DOIs
出版狀態已發佈 - 二月 1 2013
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 放射學、核子醫學和影像學
  • 癌症研究

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