Matrix metalloprotease–14 is a target enzyme for detecting peritoneal metastasis in gastric cancer

Background: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease–14 (MMP–14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. Methods: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP–14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP–14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). Results: MMP–14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64–24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53–3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP–14 group had a significantly poorer OS rate than the low expression of the MMP–14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05–5.45; P = 0.04). Conclusion: MMP–14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.