MP39-04 LARGEN PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS AND IS A PROGNOSTIC FACTOR IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-04 LARGEN PLAYS IMPORTANT ROLES IN MALIGNANT AGGRESSIVENESS AND IS A PROGNOSTIC FACTOR IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA Yasuyoshi Miyata, Yuta Mukae, Tomohiro Matsuo, Tsuyoshi Matsuda, Junki Harada, Asato Otsubo, Kensuke Mitsunari, Kojiro Ohba, Hideki Sakai, and Kazuo Yamamoto Yasuyoshi MiyataYasuyoshi Miyata More articles by this author , Yuta MukaeYuta Mukae More articles by this author , Tomohiro MatsuoTomohiro Matsuo More articles by this author , Tsuyoshi MatsudaTsuyoshi Matsuda More articles by this author , Junki HaradaJunki Harada More articles by this author , Asato OtsuboAsato Otsubo More articles by this author , Kensuke MitsunariKensuke Mitsunari More articles by this author , Kojiro OhbaKojiro Ohba More articles by this author , Hideki SakaiHideki Sakai More articles by this author , and Kazuo YamamotoKazuo Yamamoto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mitochondria is recognized as a key player in the biosynthetic and energetic capabilities of cells. Largen has been identified as a controller of cell size in mammalian cells via the regulation of mitochondrial function. Therefore, we speculated that Largen played important roles for cancer cell survival of renal cell carcinoma (RCC) via regulation of energy and cancer-related protein synthesis. The aim of this study was to clarify the pathological significance and prognostic roles of Largen in patients with clear cell (cc) RCC. METHODS: The immunoreactivity of Largen was investigated in 192 ccRCC and 60 normal kidney tissues by immunohistochemical technique. In addition, we measured proliferation index (PI) and apoptotic index (AI) using anti-Ki-67 antibody and anti-cleaved caspase-3, respectively. Tumor necrosis was evaluated by receptor-interacting protein kinase (RIP) 3 expression. Moreover, in human RCC cell lines (ACHN and 780-O), Largen expression was knocked down using small interfering RNA and the resulting changes in cell survival, migration, and invasion were investigated. RESULTS: In vitro studies showed that Largen knock-down led to the stimulation of cell death, but not to suppression of cell proliferation, migration, and invasion. In ccRCC patients, Largen expression was significantly higher in cancer tissues than in normal kidney tissues (mean±SD of IRS: 3.2 ± 1.7 vs 1.2±1.1; p<0.001). Largen expression was positively correlated with tumor grade (grade 1=2.3±1.3, grade 2=3.4±1.6, and grade 3/4=4.7±1.4; p<0.001), pT stage (p<0.001), and the presence of metastasis (p<0.001). Kaplan-Meier survival curves showed that a higher Largen IRS was a significant predictor of shorter overall survival time (p<0.001) and multivariate analyses showed that it was an independent predictor (hazard ratio=1.53, 95% confidential interval (CI)=1.24–1.91, p<0.001). Univariate analyses showed that Largen was positively correlated with PI (p<0.001) and it was negatively correlated with AI (p<0.001) and tumor necrosis (p=0.024). However, multi-variate analyses adjusted by pathological features showed Largen was independently associated with tumor necrosis (odds ratio=0.35, 95% CI= 0.17–0.75, p=0.007), but not with PI and AI. CONCLUSIONS: Largen played important roles in malignant aggressiveness and was a prognostic indicator, due to its regulation of tumor necrosis in patients with ccRCC. Finally, we propose that Largen is a novel therapeutic target and useful predictor in these patients. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e705-e705 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuyoshi Miyata More articles by this author Yuta Mukae More articles by this author Tomohiro Matsuo More articles by this author Tsuyoshi Matsuda More articles by this author Junki Harada More articles by this author Asato Otsubo More articles by this author Kensuke Mitsunari More articles by this author Kojiro Ohba More articles by this author Hideki Sakai More articles by this author Kazuo Yamamoto More articles by this author Expand All Advertisement Loading ...