MP65-01 4N1K-PEPTIDE DERIVED FROM THROMBOSPONIDN-2 IS ASSOCIATED WITH MALIGNANT AGGRESSIVENESS AND PROGNOSIS IN BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2018MP65-01 4N1K-PEPTIDE DERIVED FROM THROMBOSPONIDN-2 IS ASSOCIATED WITH MALIGNANT AGGRESSIVENESS AND PROGNOSIS IN BLADDER CANCER Yasuyoshi Miyata, Tsutomu Yuno, Kyohei Araki, Yuichiro Nakamura, Takuji Yasuda, Yuji Sagara, Tomohiro Matsuo, Kojiro Ohba, and Hideki Sakai Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Tsutomu YunoTsutomu Yuno More articles by this author , Kyohei ArakiKyohei Araki More articles by this author , Yuichiro NakamuraYuichiro Nakamura More articles by this author , Takuji YasudaTakuji Yasuda More articles by this author , Yuji SagaraYuji Sagara More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , Kojiro OhbaKojiro Ohba More articles by this author , and Hideki SakaiHideki Sakai More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2067AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Thrombospondins (TSPs) play various important roles under pathological conditions. TSP-1 is well-known and recognised as strong angiogenesis inhibitors in various types of cancers. The 4N1K-peptide (KRFYVVMWKK) is reported to be derived from TSP-1 and TSP-2, and its expression was significantly associated with tumor progression and survival in several cancers. In contrast to TSP-1, pathological significance of TSP-2 and 4N1K-peptide in bladder cancer (BC) are not clear. The main aim is to clarify the pathological roles of TSP-2 and 4N1K-peptide in BC because fewer studies have evaluated them in these patients. METHODS We immunohistochemically examined 206 BC tissues for TSP-2, and 4N1K-peptide expressions. Their independent contributions to cancer cell proliferation were measured by anti-Ki-67 antibody; apoptosis was measured by anti-cleaved caspase-3 antibody; angiogenesis was measured by anti-CD34 antibody, and MMP-9 immunoreactivity was also examined in these tissues. RESULTS TSP-2 expression was negatively associated with T stage (P < 0.001), metastasis (P = 0.021), and grade (P = 0.018). Similar negative relationships were also detected with respect to 4N1K-peptide expression (P < 0.001, 0.025, and 0.002, respectively). TSP-2 expression was negatively associated with cell proliferation (P = 0.005) and MMP-9 expression (P < 0.001), whereas 4N1K-peptide was significantly associated with apoptosis (P < 0.001), angiogenesis (P = 0.024), and MMP-9 expression (P = 0.005). Subsequently, when the independent role of TSP-2 or 4N1K-peptide was investigated by using a multivariate analysis model, including all pathological features, TSP-2 expression was significantly associated with MMP-9 expression (odds ratio = 0.33, 95% confidential interval, CI = 0.17–0.64, P = 0.001). A similar independent correlation was detected between 4N1K-peptide expression and MVD (odds ratio = 0.52, 95% CI = 0.29–0.95, P = 0.033). In survival analyses, multivariate analyses showed that 4N1K-peptide expression was a significant predictor for subsequent metastasis (hazard ratio, HR = 3.90, 95% CI = 1.68–9.07, P = 0.002) and overall survival (HR = 2.43, 95% CI = 1.12–4.86, P = 0.012). CONCLUSIONS Our results demonstrated that TSP-2 and 4N1K-peptide played important roles in the malignant aggressiveness and progression of BC via complex mechanisms involving cell proliferation, apoptosis, angiogenesis, and MMP-9 expression. We suggested that TSP-2 and 4N1K-peptide are potential therapeutic targets and useful predictor for prognosis in patients with BC. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e858-e859 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Yasuyoshi Miyata More articles by this author Tsutomu Yuno More articles by this author Kyohei Araki More articles by this author Yuichiro Nakamura More articles by this author Takuji Yasuda More articles by this author Yuji Sagara More articles by this author Tomohiro Matsuo More articles by this author Kojiro Ohba More articles by this author Hideki Sakai More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...