8�C15.5%,26 2.3�C13.3%27 and 3�C10%,26, 28 respectively, suggesting that, in some cases, such information tumors amplify these regions for selective advantage. Combined expression of these three genes could predict overall survival and time to progression of CF-treated gastric cancer patients. Thus, combining array CGH analysis with relevant transcriptional changes is a feasible approach for building a predictive model using functionally important genes and reducing the likelihood of false biomarker discovery. Transcriptional levels of genes other than MYC, EGFR and FGFR2 identified in the amplified genomic loci were not associated with the survival of the 96 training set patients (for example, P=0.313 for ERBB2).
Primary gastric tumors are not easily measurable by current radiographic techniques, and often there are no metastatic lesions that are readily quantifiable in metastatic gastric cancer patients. To develop a predictor from the general population of gastric cancer patients in an unbiased way, this study was designed to correlate gene expression profiling of the tumors with overall survival and time to progression, not radiographic response. Overall survival is the ultimate measure of the treatment benefit afforded to a patient and is a particularly appropriate gauge for patients with metastatic gastric cancer, as radiographic assessment is problematic in such patients. The fact that both the time to progression as well as overall survival are predicted by our three-gene predictor in CF-treated patients, but not surgically treated patients, suggests that the three-gene predictor is a predictive indicator for the clinical benefit from CF.
Although EGFR and FGFR2 expression have been reported to have prognostic value for gastric cancer patients treated surgically,29, 30 we did not find the three-gene predictive index to be prognostic for surgically treated patients with gastric cancer. Our findings are consistent with previously reported experimental data on chemoresistance. Inhibitors of EGFR act synergistically with cisplatin31 and fluorouracil,32 whereas an FGFR2 inhibitor is synergistic with fluorouracil.33 MYC has been linked to cisplatin resistance in several in vitro models.34, 35, 36, 37 Taken together, combined expression of MYC, EGFR and FGFR2 is predictive of poor survival in CF-treated metastatic gastric cancer patients.
More focused prospective trials that are designed to test the clinical utility of this three-gene predictor are warranted. Acknowledgments The work was supported in part by National Institute Dacomitinib of Health Intramural Program, Center for Cancer Research, National Cancer Institute, Korean National Cancer Center Grant 0910570 and Converging Research Center Program through the Ministry of Education, Science and Technology of Korea (2010K001121).