Mp05-09 a Novel Method to Identify Aggressive Prostate Cancer With Dna-Methylation Signatures From Prostate Needle Biopsy

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-09 A NOVEL METHOD TO IDENTIFY AGGRESSIVE PROSTATE CANCER WITH DNA-METHYLATION SIGNATURES FROM PROSTATE NEEDLE BIOPSY Masatomo Kaneko, Yohei Sekino, Hongtao Li, Xinyi Zhou, Mingda Jin, Wei Guo, Xiaojing Yang, Jeffrey Bhasin, Atsuko Fujihara, Tsuyoshi Iwata, Lorenzo Storino Ramacciotti, Divyangi Paralkar, Giovanni E. Cacciamani, Manju Aron, Osamu Ukimura, Inderbir S. Gill, Gangning Liang, and Andre Luis Abreu Masatomo KanekoMasatomo Kaneko , Yohei SekinoYohei Sekino , Hongtao LiHongtao Li , Xinyi ZhouXinyi Zhou , Mingda JinMingda Jin , Wei GuoWei Guo , Xiaojing YangXiaojing Yang , Jeffrey BhasinJeffrey Bhasin , Atsuko FujiharaAtsuko Fujihara , Tsuyoshi IwataTsuyoshi Iwata , Lorenzo Storino RamacciottiLorenzo Storino Ramacciotti , Divyangi ParalkarDivyangi Paralkar , Giovanni E. CacciamaniGiovanni E. Cacciamani , Manju AronManju Aron , Osamu UkimuraOsamu Ukimura , Inderbir S. GillInderbir S. Gill , Gangning LiangGangning Liang , and Andre Luis AbreuAndre Luis Abreu View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To discover DNA-methylation signatures associated with clinically significant prostate cancer (CSPCa, grade group GG ≥2) on prostate biopsy (PBx). METHODS: Patients undergoing radical prostatectomy (RP) for prostate cancer (PCa) from April 2019 to July 2022 were prospectively recruited (IRB# HS-16-00404). Patients who underwent previous treatment for PCa were excluded. Two-core PBx fresh tissue was precisely sampled from the same location in the right and left lobes of the ex-vivo RP specimen (total 4-core per-patient). Then, one-core each was histopathologically (H&E) analyzed, and the other core was processed using Simplified Whole-panel Amplification Reaction Method (SWARM®) a robust targeted bisulfite sequencing approach. From 396,020 CpG sites (CpGs) related to PCa, 1254CpGs were selected for the analysis. The ex-vivo PBx histopathology was used as ground truth for paired-cores to identify methylation CpG sites (CpGs) strongly associated with CSPCa. The multi-class (benign vs GG1 vs CSPCa) discriminating performance was analyzed with a random forest. The samples were randomly separated at a 6:4 ratio into training and testing datasets. The area under the receiver operating characteristic curve (AUC) and diagnostic performance at Youden index on the testing dataset were reported. RESULTS: A total of 334 ex-vivo PBx cores (205 training vs 129 testing) acquired from 149 participants were included. The median age, PSA, and PSA density were 65 years, 6.7ng/mL, and 0.14ng/mL2, respectively. The index lesion on RP histology was GG1 (6.0%), 2 (52%), 3 (25%), 4 (4.0%), and 5 (12%). Benign tissue, GG1 and CSPCa were sampled in 230 (69%), 27 (8.1%) and 77 (23%) ex-vivo biopsy cores, respectively. Individual 44 CpGs as a feature in classifying PCa showed an average AUC of 0.80. The combined set of 44 CpGs achieved AUC 0.88 for PCa detection. Among them, the combination of top 12 CpGs showed AUC of 0.87, sensitivity of 78%, and specificity of 90% for CSPCa detection (Figure 1). CONCLUSIONS: Twelve DNA-methylation CpGs associated with CSPCa were successfully identified in PBx. This novel methodology presents the potential to distinguish patients with poor prognoses from PBx. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e46 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Masatomo Kaneko More articles by this author Yohei Sekino More articles by this author Hongtao Li More articles by this author Xinyi Zhou More articles by this author Mingda Jin More articles by this author Wei Guo More articles by this author Xiaojing Yang More articles by this author Jeffrey Bhasin More articles by this author Atsuko Fujihara More articles by this author Tsuyoshi Iwata More articles by this author Lorenzo Storino Ramacciotti More articles by this author Divyangi Paralkar More articles by this author Giovanni E. Cacciamani More articles by this author Manju Aron More articles by this author Osamu Ukimura More articles by this author Inderbir S. Gill More articles by this author Gangning Liang More articles by this author Andre Luis Abreu More articles by this author Expand All Advertisement PDF downloadLoading ...