期刊
PHARMACOGENOMICS JOURNAL
卷 10, 期 4, 页码 267-277出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2010.33
关键词
prediction; acetaminophen; blood; cross-tissue; liver injury; microarray gene expression
资金
- Oak Ridge Institute for Science and Education (ORISE) at the National Center for Toxicological Research (NCTR), US Food and Drug Administration (FDA)
- China State
- Chinese Key Technologies RD Program [2005CB23402]
- National Science Foundation of China at the NCTR/FDA [30801556]
- Intramural Research Program of the NIH
- NIEHS [Z01 ES102345-03]
Genomic biomarkers for the detection of drug-induced liver injury (DILI) from blood are urgently needed for monitoring drug safety. We used a unique data set as part of the Food and Drug Administration led MicroArray Quality Control Phase-II (MAQC-II) project consisting of gene expression data from the two tissues (blood and liver) to test cross-tissue predictability of genomic indicators to a form of chemically induced liver injury. We then use the genomic indicators from the blood as biomarkers for prediction of acetaminophen-induced liver injury and show that the cross-tissue predictability of a response to the pharmaceutical agent (accuracy as high as 92.1%) is better than, or at least comparable to, that of non-therapeutic compounds. We provide a database of gene expression for the highly informative predictors, which brings biological context to the possible mechanisms involved in DILI. Pathway-based predictors were associated with inflammation, angiogenesis, Toll-like receptor signaling, apoptosis, and mitochondrial damage. The results show for the first time and support the hypothesis that genomic indicators in the blood can serve as potential diagnostic biomarkers predictive of DILI. The Pharmacogenomics Journal (2010) 10, 267-277; doi: 10.1038/tpj.2010.33
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