Pd17-09 cd70-positive extracellular vesicles for detection of clear-cell renal cell carcinoma

You have accessJournal of UrologyCME1 Apr 2023PD17-09 CD70-POSITIVE EXTRACELLULAR VESICLES FOR DETECTION OF CLEAR-CELL RENAL CELL CARCINOMA Rodrigo R. Pessoa, Reza Nabavizadeh, Ali Arafa, Roxane Lavoie, Yohan Kim, Liguo Wang, Jeanette Eckel-Passow, Bradley C. Leibovich, and Fabrice Lucien Rodrigo R. PessoaRodrigo R. Pessoa More articles by this author , Reza NabavizadehReza Nabavizadeh More articles by this author , Ali ArafaAli Arafa More articles by this author , Roxane LavoieRoxane Lavoie More articles by this author , Yohan KimYohan Kim More articles by this author , Liguo WangLiguo Wang More articles by this author , Jeanette Eckel-PassowJeanette Eckel-Passow More articles by this author , Bradley C. LeibovichBradley C. Leibovich More articles by this author , and Fabrice LucienFabrice Lucien More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: One third of patients treated for localized clear-cell renal cell carcinoma (ccRCC) will eventually develop recurrent disease after surgery. Identification of patients who may benefit from intensification of care with adjuvant therapy is an important unmet need. Tumor-derived extracellular vesicles (EVs), microscopic particles released by tumor cells, have emerged as a potential biomarker in other malignancies but have not been studied in kidney cancer. Herein, we sought to characterize tumor specific EVs levels among patients undergoing radical nephrectomy for ccRCC. METHODS: We employed in silico multi-omic analysis of ccRCC tumors using TCGA KIRC (N=537 patients), CPTAC (N= 103 patients) and GTEx (N= 948 donors) to identify CD70, an integral membrane protein, as the top marker candidate for ccRCC-derived EVs. Expression of CD70+ in ccRCC-derived EVs was confirmed using freshly isolated tumor specimens. Blood levels of circulating CD70+-EVs were measured using high resolution flow cytometry in a cohort of age-matched healthy donors (HD) (N=15) and ccRCC patients (N=29) treated with radical nephrectomy. EVs levels between HD and RCC patients were compared using ANOVA test. Association between patient characteristics and EVs levels was analyzed using Pearson’s correlation and Fisher’s exact test. RESULTS: Blood levels of CD70+-EVs were significantly elevated in patients with pT1-T2 (median: 4.3×106 per mL, p<0.01) and pT3-T4 (median: 6.0×106, p<0.001) ccRCC compared with HD (median: 0.4×106, Figure 1A). High CD70+-EVs levels were associated with pT3-T4 stage (Figure 1B, p<0.0001).There was a strong positive correlation between CD70+-EVs at diagnosis and tumor size (Pearson r=0.76, p<0.0001, Figure 1C). Radical nephrectomy was associated with reduction in CD70+-EVs levels in 83.8% of patients (Figure 1D, p=0.0076). CONCLUSIONS: Patients with ccRCC, in particular those with larger and more advanced stage tumors, have high levels of circulating CD70+-EVs, which decreases significantly after surgery. CD70+-EVs levels are a marker of tumor burden in ccRCC and could be further explored as a biomarker for risk-stratification and selection of patients for additional treatment after radical nephrectomy for ccRCC. Source of Funding: Eagles 5th District Cancer Telethon - Cancer Research Fund (FL) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e499 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rodrigo R. Pessoa More articles by this author Reza Nabavizadeh More articles by this author Ali Arafa More articles by this author Roxane Lavoie More articles by this author Yohan Kim More articles by this author Liguo Wang More articles by this author Jeanette Eckel-Passow More articles by this author Bradley C. Leibovich More articles by this author Fabrice Lucien More articles by this author Expand All Advertisement PDF downloadLoading ...