Introduction: 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: 4.3x106 per mL, p<0.01) and pT3-T4 (median: 6.0x106, p<0.001) ccRCC compared with HD (median: 0.4x106, Fig.1A). High CD70+-EVs levels were associated with pT3-T4 stage (Fig.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, Fig.1C). Radical nephrectomy was associated with reduction in CD70+-EVs levels in 83.8% of patients (Fig.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)
