title: Three-gene predictor of clinical outcome for gastric cancer patients treated with chemotherapy.
abstract: 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.
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Kim
authors.forename: I J
authors.initials: IJ
authors.lastname: Choi
authors.forename: C G
authors.initials: CG
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Oshima
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Arao
authors.forename: K
authors.initials: K
authors.lastname: Nishio
authors.forename: A
authors.initials: A
authors.lastname: Michalowski
authors.forename: J E
authors.initials: JE
authors.lastname: Green
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D016259:Genes, myc; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2