Evaluation of prognostic factors for the response to S-1 in patients with stage II or III advanced gastric cancer who underwent gastrectomy

Objectives Many studies have reported that low intratumoral mRNA expression of thymidylate synthase (TS) is an important biomarker of response to chemotherapy in patients with unresectable advanced gastric cancer. However, the role of gene expression profile of patients who received postoperative adjuvant chemotherapy remains unclear. In this study, we evaluated how TS and other associated genes related to outcome. Methods Seventy-nine patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed. Thirty-nine patients received adjuvant chemotherapy with S-1 after surgery (S-1 group) and 40 patients underwent surgery only (surgery group). Formalin-fixed, paraffin-embedded tumor tissues were dissected by the laser-captured microdissection technique and analyzed for target gene expressions using a quantitative real-time polymerase chain reaction. Results There were no significant differences between the S-1 group and the surgery group in gene expressions except TS (P=0.034). In the S-1 group, recurrence-free survival (RFS) and overall survival (OS) were significantly longer in patients with low TS expression compared with patients with high TS expression (P=0.021 and 0.016), whereas there were no correlations in the surgery group. Furthermore, RFS and OS were both correlated with extent of lymph node metastasis (N) (P=0.038 and 0.020) and TS expression (P=0.021 and 0.032). On multivariate analysis it was found that TS expression and N were significant independent prognostic factors of RFS and OS (TS: P=0.027 and 0.050, N: P=0.048 and 0.032). Conclusion Our results suggested that intratumoral TS expression is an independent prognostic factor in patients with gastric cancer who received postoperative adjuvant chemotherapy with S-1. Pharmacogenetics and Genomics 19:955-964 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.