MP57-17 PROGNOSTIC IMPACT OF PHOSPHATIDYLINOSITOL PHOSPHATE AND ITS ASSOCIATED ENZYME LEVELS IN PATIENTS WITH RENAL CELL CARCINOMA TREATED SURGICALLY

Abstract

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy IV (MP57)1 Apr 2020MP57-17 PROGNOSTIC IMPACT OF PHOSPHATIDYLINOSITOL PHOSPHATE AND ITS ASSOCIATED ENZYME LEVELS IN PATIENTS WITH RENAL CELL CARCINOMA TREATED SURGICALLY Shintaro Narita*, Hiroki Nakanishi, Yoshinori Matsuda, Huang Mingguo, Mizuki Kobayashi, Akane Kikuchi, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Atsushi Koizumi, Mitsuru Saito, Takamitsu Inoue, Shigeru Satoh, Takehiko Sasaki, and Tomonori Habuchi Shintaro Narita*Shintaro Narita* More articles by this author , Hiroki NakanishiHiroki Nakanishi More articles by this author , Yoshinori MatsudaYoshinori Matsuda More articles by this author , Huang MingguoHuang Mingguo More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Akane KikuchiAkane Kikuchi More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Sohei KandaSohei Kanda More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Atsushi KoizumiAtsushi Koizumi More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Takehiko SasakiTakehiko Sasaki More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000926.017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The phosphoinositide (PIP) is associated with the risk of developing renal cell carcinoma (RCC). However, the levels of lipid metabolites, including PIPs phosphate derivatives, in patients with RCC is unknown. Thus, we investigated the PIP profile and its impact on clinical outcomes in patients with RCC who underwent surgery. METHODS: A total of 85 patients with RCC treated with surgery between 2011 and 2014 were included. The level of PIPs (PI, PIP1 and PIP2) in the tumor and its surrounding normal tissues was assessed by LC–MS–MS using a selected reaction monitoring with electrospray ionization. The mRNA expression of 16 phosphatases associated with the PIPs in the tumor was measured by qRT–PCR. RESULTS: No significant difference was observed in the PIP level between the tumors and normal surrounding tissues. The patients with high-grade tumor had significantly lower PIP1 and PIP2 (C38:4) tumor-to-normal (T/N) ratio than those with low-grade tumor. The metastatic-free survival (MFS) of patients with low PIP1 and PIP2 (C38:4) T/N ratios was significantly lower than that of patients with high PIP1 and/or PIP2 (C38:4) T/N ratios (p = 0.007). However, no significant difference was observed in the cancer-specific survival between the two groups (p = 0.590). The 5-year MFS of patients with low PIP1 and PIP2 (C38:4) T/N ratios was 67.0% and that of patients with either high PIP1 or PIP2 T/N ratio was 96.2%. In a multivariable analysis, pT stage and low PIP1 and PIP2 T/N ratios were found to be the independent prognostic factors of poor MFS in patients with RCC who underwent surgery (hazard ratio [HR] = 6.8, p = 0.015 and HR = 9.23, p = 0.041, respectively). Several candidate phosphatases associated with high-grade tumor were assessed using VIP score. Among the different types of phosphatases, the T/N ratios of patients with MTM1 and MTMR6 mRNA significantly correlated with PIP1 and PIP2 (C38:4) T/N ratios. CONCLUSIONS: Low PIP1 and PIP2 (C38:4) T/N ratios are associated with cancer aggressiveness and poor MFS in patients with RCC who underwent surgery. The PIP levels in surgical specimens can be a potential biomarker of oncological outcomes in patients with RCC, and targeting the enzymes associated with PIPs may be a novel treatment strategy for RCC. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e868-e869 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shintaro Narita* More articles by this author Hiroki Nakanishi More articles by this author Yoshinori Matsuda More articles by this author Huang Mingguo More articles by this author Mizuki Kobayashi More articles by this author Akane Kikuchi More articles by this author Taketoshi Nara More articles by this author Sohei Kanda More articles by this author Kazuyuki Numakura More articles by this author Atsushi Koizumi More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Shigeru Satoh More articles by this author Takehiko Sasaki More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...