, , and are associated with hematogenous, lymph node, and peritoneal recurrence in stage II/III gastric cancer patients enrolled in the ACTS-GC study.

BACKGROUND

To identify factors related to relapse sites, we carried out an exploratory biomarker analysis of data from the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer study, which is a randomized, controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer.

PATIENTS AND METHODS

Surgical specimens from 829 patients were retrospectively examined, and 63 genes involved in a variety of biological processes were analyzed by quantitative real-time PCR. Gene expression normalized to reference genes was categorized as lower or higher than the median, and association with relapse sites was analyzed based on 5-year relapse-free survival.

RESULTS

Hematogenous, lymph node, and peritoneal recurrence developed in 72, 105, and 138 of the 829 patients, respectively; hazard ratios were 0.79 (95% confidential interval: 0.54-1.16), 0.51 (0.31-0.82), and 0.60 (0.42-0.84), respectively. Expression of platelet/endothelial cell adhesion molecule 1 (PECAM1) and topoisomerase II alpha () was strongly correlated with hematogenous recurrence and peritoneal recurrence, respectively (false discovery rate = 7.7×10 and 0.002, respectively). Gamma-glutamyl hydrolase () expression was moderately correlated with lymph node recurrence (false discovery rate = 0.34). Relapse-free survival was worse in patients expressing high levels of (hazard ratio = 2.37, 1.65-3.41), (hazard ratio = 2.35, 1.55-3.57), or (hazard ratio = 1.87, 1.13-3.08), respectively. A multivariate analysis revealed that these were stronger independent risk factors than tumor histological type.

CONCLUSION

In patients with stage II/III gastric cancer, , , and levels in primary tumors are linked to high risk of hematogenous, lymph node, and peritoneal recurrence, respectively.