Pd09-03 Assessing Epigenetic Features Associated With Lymph Node Metastases in Prostate Cancer

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD09)1 May 2024PD09-03 ASSESSING EPIGENETIC FEATURES ASSOCIATED WITH LYMPH NODE METASTASES IN PROSTATE CANCER Marco Bandini, Paolo Zaurito, Francesco Barletta, Giuseppe Ottone Cirulli, Roberta Lucianò, Francesca Giannese, Giulia Maria Scotti, Caterina Oneto, Armando Stabile, Elio Mazzone, Vito Cucchiara, Gabriele Sorce, Nazario Pio Tenace, Federico Scarfò, Giorgio Brembilla, Antonio Esposito, Marco Morelli, Dejan Lazarevic, Francesco De Cobelli, Claudio Doglioni, Giovanni Tonon, Alberto Briganti, Giorgio Gandaglia, and Francesco Montorsi Marco BandiniMarco Bandini , Paolo ZauritoPaolo Zaurito , Francesco BarlettaFrancesco Barletta , Giuseppe Ottone CirulliGiuseppe Ottone Cirulli , Roberta LucianòRoberta Lucianò , Francesca GianneseFrancesca Giannese , Giulia Maria ScottiGiulia Maria Scotti , Caterina OnetoCaterina Oneto , Armando StabileArmando Stabile , Elio MazzoneElio Mazzone , Vito CucchiaraVito Cucchiara , Gabriele SorceGabriele Sorce , Nazario Pio TenaceNazario Pio Tenace , Federico ScarfòFederico Scarfò , Giorgio BrembillaGiorgio Brembilla , Antonio EspositoAntonio Esposito , Marco MorelliMarco Morelli , Dejan LazarevicDejan Lazarevic , Francesco De CobelliFrancesco De Cobelli , Claudio DoglioniClaudio Doglioni , Giovanni TononGiovanni Tonon , Alberto BrigantiAlberto Briganti , Giorgio GandagliaGiorgio Gandaglia , and Francesco MontorsiFrancesco Montorsi View All Author Informationhttps://doi.org/10.1097/01.JU.0001008572.33286.63.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prediction of lymph node invasion (LNI) is pivotal in prostate cancer (PCa) patients eligible for radical prostatectomy (RP). Tumor DNA methylation has been proposed as driving factor for LNI. None of the available epigenetic signatures predicting LNI have been validated using lymph node metastasis. This study aimed to test and validate two epigenetic signatures developed from MRI visible and invisible tumor biopsy lesions within the DNA of PCa nodal metastases. METHODS: A total of 172 men diagnosed with cN0M0 PCa treated with RP and ePLND at a tertiary referral center were identified. We extracted the DNA from FFPE samples of tumor and healthy tissue specimens. To determine the methylation status of CpG reach areas, we performed DNA methylome profiling using reduced representation bisulfite sequencing (RRBS). Two epigenetic signatures that were initially developed in the same group of patients using both tumor target and systematic biopsy specimens were validated in samples from lymph node metastases and healthy prostatic tissues. We compared the methylation patterns of CpG sites previously linked to LNI between biopsy samples (both target and systematic) with PCa, lymph node metastases, and healthy tissue samples. Differences in average methylation levels were assessed using a Student's t-test. RESULTS: A total of 508 and 511 highly differentially methylated CpGs sites within MRI-targeted and systematic samples associated with LNI were identified. Significant differences emerged between the average methylation signals within hypomethylated CpGs of nodal metastases with controls (p=0.03) and target core samples from patients without LNI (p=0.01). Additionally, significant differences were observed when comparing target core samples from patients with LNI with controls (p<0.001) and target core samples from patients without LNI (p<0.001). No difference was observed between nodal metastases and target core samples with LNI (p=0.03). This trend was not observed in the comparison of hypermethylated CpGs between target biopsy samples from patients with LNI, nodal metastases, and controls. Similarly, no differences were found in the comparison of both hypermethylated and hypomethylated CpGs among systematic cores, nodal samples, and controls. CONCLUSIONS: Only CpG sites previously identified as hypomethylated exhibited significant hypomethylation in nodal metastases compared to controls and target samples of patients without LNI. Average methylation signals were similar between nodal metastases and target core samples with LNI. Reduced methylation within target samples may be involved in the development of LNI. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e180 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Marco Bandini More articles by this author Paolo Zaurito More articles by this author Francesco Barletta More articles by this author Giuseppe Ottone Cirulli More articles by this author Roberta Lucianò More articles by this author Francesca Giannese More articles by this author Giulia Maria Scotti More articles by this author Caterina Oneto More articles by this author Armando Stabile More articles by this author Elio Mazzone More articles by this author Vito Cucchiara More articles by this author Gabriele Sorce More articles by this author Nazario Pio Tenace More articles by this author Federico Scarfò More articles by this author Giorgio Brembilla More articles by this author Antonio Esposito More articles by this author Marco Morelli More articles by this author Dejan Lazarevic More articles by this author Francesco De Cobelli More articles by this author Claudio Doglioni More articles by this author Giovanni Tonon More articles by this author Alberto Briganti More articles by this author Giorgio Gandaglia More articles by this author Francesco Montorsi More articles by this author Expand All Advertisement PDF downloadLoading ...