Mp05-07 Gdf15 Propeptide Is a Novel Blood Biomarker for Castration-Resistant Prostate Cancer With Bone Metastasis via Promoting the Vicious Cycle

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-07 GDF15 PROPEPTIDE IS A NOVEL BLOOD BIOMARKER FOR CASTRATION-RESISTANT PROSTATE CANCER WITH BONE METASTASIS VIA PROMOTING THE VICIOUS CYCLE Gaku Yamamichi, Taigo Kato, Noriaki Arakawa, Yuichi Motoyama, Hidetatsu Outani, Shohei Myoba, Yu Ishizuya, Yoshiyuki Yamamoto, Koji Hatano, Atsunari Kawashima, Hiroji Uemura, Motohide Uemura, and Norio Nonomura Gaku YamamichiGaku Yamamichi , Taigo KatoTaigo Kato , Noriaki ArakawaNoriaki Arakawa , Yuichi MotoyamaYuichi Motoyama , Hidetatsu OutaniHidetatsu Outani , Shohei MyobaShohei Myoba , Yu IshizuyaYu Ishizuya , Yoshiyuki YamamotoYoshiyuki Yamamoto , Koji HatanoKoji Hatano , Atsunari KawashimaAtsunari Kawashima , Hiroji UemuraHiroji Uemura , Motohide UemuraMotohide Uemura , and Norio NonomuraNorio Nonomura View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is no useful blood biomarker for bone metastases (BM) in prostate cancer (PCa). Especially in castration-resistant prostate cancer (CRPC), bone scan index (BSI) by bone scintigraphy is a more accurate indicator of BM than PSA. However, this imagical inspection is only available in a limited number of facilities, so the purpose of this study was to create a simple and sensitive BM biomarker for CRPC patients. METHODS: We comprehensively examine culture supernatants from 7 prostate, 4 kidney, and 4 bladder cancer cell lines using Orbitrap LC-MS to identify a protein specifically secreted by PCa and has not been previously reported as a biomarker. The effects of this protein will be examined in PCa cells (PC-3 and DU145), osteoblasts, osteoclasts. To evaluate the mechanism of the protein, we injected luciferase gene-transfected PC3 to the tibia of NOD/SCID mice to create BM model. In addition, plasma concentrations of this protein will be measured by ELISA in 185 patients, including 80 mCRPC patients for whom BSI is being measured, and compared with existing biomarkers (PSA, ALP, LDH, OC, BAP, PINP, TRACP 5b). RESULTS: A total of 2,167 proteins were identified by secretome analysis, and we focused on GDF15 propeptide (GDPP), which is secreted by osteoblasts and osteoclasts as well as PCa cells, and promotes proliferation, migration, and invasive ability in PC3 and DU145. Furthermore, GDPP enhanced bone formation via increased expression of RUNX2, OSX, and ATF4 in osteoblasts, and enhanced bone resorption via increased expression of NFATc1 and DC-STAMP in osteoclasts. In BM mouse model, GDPP aggravated BM with increasing of osteoblast and osteoclast expression (Figure 1). Clinical performance in two cohorts showed that GDPP (both AUC=0.92) was more diagnostic for BM than PSA (AUC=0.78 and 0.59) (Figure 2). The amount of change in BSI over time with systemic treatment clearly correlated with that of GDPP (r=0.67), but not with that of PSA (r=-0.041). CONCLUSIONS: GDPP enhances the vicious cycle in the bone microenvironment and is a novel blood biomarker reflecting the aggressiveness of BM in CRPC patients. Download PPTDownload PPT Source of Funding: KAKENHI grant (21K09396 and 20K23002) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e45 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Gaku Yamamichi More articles by this author Taigo Kato More articles by this author Noriaki Arakawa More articles by this author Yuichi Motoyama More articles by this author Hidetatsu Outani More articles by this author Shohei Myoba More articles by this author Yu Ishizuya More articles by this author Yoshiyuki Yamamoto More articles by this author Koji Hatano More articles by this author Atsunari Kawashima More articles by this author Hiroji Uemura More articles by this author Motohide Uemura More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ...