Methylated TMS1 and DAPK genes predict prognosis and response to chemotherapy in gastric cancer

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis-related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation-specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMSI and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5-fluorouracil-based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMSI: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMSI: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer. (c) 2007 Wiley-Liss, Inc.