Abstract 1924: Urine extracellular vesicles derived CA9 and CIZ1 as non-invasive biomarkers for early diagnosis of clear cell renal cell carcinoma

Abstract Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, with clear cell renal cell carcinoma (ccRCC) being the most prevalent pathological subtype. Metastasis is observed in 20-30% of patients at initial diagnosis, and 20% of cases develop metastasis even after surgery, resulting in poor prognosis due to insensitivity to radiotherapy and chemotherapy. Early and accurate diagnosis is critical to improving outcomes and survival rates. However, specific humoral markers for non-invasive early screening and diagnosis of RCC are currently lacking. Urinary extracellular vesicles (EVs) have emerged as promising biomarkers for urinary system diseases due to their stability and ease of collection. In this study, we conducted a comprehensive analysis of urine EVs to identify specific biomarkers for ccRCC. Urine samples were collected from 100 healthy donors, 100 renal cyst patients, and 300 RCC patients (200 ccRCC, 50 papillary RCC [pRCC], and 50 chromophobe RCC [chRCC]). Agglutinin-coupled magnetic beads were employed to enrich exosomes, followed by proteomic analysis to identify differential protein expression. Results revealed significant upregulation of CA9 and CIZ1 proteins in urine EVs from ccRCC patients compared to controls. Importantly, these proteins were elevated in early-stage and small-sized ccRCC cases. Stability testing demonstrated that CA9 and CIZ1 proteins in EVs maintained stability over time and increased with urine volume. Diagnostic efficacy was evaluated in a larger cohort (1, 500 cases) using receiver operating characteristic (ROC) curve analysis. CA9 and CIZ1 achieved area under the curve (AUC) values of 0.8917 and 0.8843, respectively, in distinguishing ccRCC from normal and other RCC cases. A combined model of the two markers achieved the highest discriminative power, with an AUC of 0.9633, sensitivity of 96.52%, and specificity of 86.69%. This study highlights the potential of CA9 and CIZ1 in urine-derived EVs as non-invasive biomarkers for ccRCC diagnosis. These findings provide a foundation for novel early screening methods and lay the groundwork for future research to validate these biomarkers in larger cohorts and investigate their stage-specific expression, ultimately facilitating personalized diagnosis and treatment of ccRCC. Citation Format: Xiyi Wei, Xi Zhang, Xinghan Yan, Zijie Yu, Weiyu Kong, Yize Li, Chao Qin, Hongwei Liang. Urine extracellular vesicles derived CA9 and CIZ1 as non-invasive biomarkers for early diagnosis of clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1924.