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

Soichiro Ogawa, Hidemasa Kubo, Yasutoshi Murayama, Takeshi Kubota, Masayuki Yubakami, Tatsuya Matsumoto, Takuma Ohashi, Kazuma Okamoto, Yugo Kuriki, Kenjiro Hanaoka, Yasuteru Urano, Eigo Otsuji

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1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number102420
JournalPhotodiagnosis and Photodynamic Therapy
Volume35
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • fluorescence imaging
  • gastric cancer
  • matrix metalloprotease–14
  • peritoneal metastasis

ASJC Scopus subject areas

  • Biophysics
  • Oncology
  • Dermatology
  • Pharmacology (medical)

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