Journal
PHARMACOGENOMICS JOURNAL
Volume 12, Issue 2, Pages 119-127Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/tpj.2010.87
Keywords
gastric; cancer; chemotherapy; gene; expression
Categories
Funding
- National Institute of Health
- Center for Cancer Research
- National Cancer Institute
- Korean National Cancer Center [0910570]
- Ministry of Education, Science and Technology of Korea [2010K001121]
- Grants-in-Aid for Scientific Research [23701106] Funding Source: KAKEN
- Korea Health Promotion Institute [0910570] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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To identify transcriptional profiles predictive of the clinical benefit of cisplatin and fluorouracil (CF) chemotherapy to gastric cancer patients, endoscopic biopsy samples from 96 CF-treated metastatic gastric cancer patients were prospectively collected before therapy and analyzed using high-throughput transcriptional profiling and array comparative genomic hybridization. Transcriptional profiling identified 917 genes that are correlated with poor patient survival after CF at P<0.05 (poor prognosis signature), in which protein synthesis and DNA replication/recombination/repair functional categories are enriched. A survival risk predictor was then constructed using genes, which are included in the poor prognosis signature and are contained within identified genomic amplicons. The combined expression of three genes-MYC, EGFR and FGFR2-was an independent predictor for overall survival of 27 CF-treated patients in the validation set (adjusted P = 0.017), and also for survival of 40 chemotherapy-treated gastric cancer patients in a published data set (adjusted P = 0.026). Thus, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients. The Pharmacogenomics Journal (2012) 12, 119-127; doi:10.1038/tpj.2010.87; published online 21 December 2010
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