A Multivariate Diagnostic Model Based on Urinary EpCAM-CD9 Positive Extracellular Vesicles for Prostate Cancer Diagnosis

Abstract

Background: Prostate cancer (PCa) is one of the most frequently diagnosed cancers and the leading cause of cancer death in males worldwide. However, current biomarkers used in the clinic such as prostate-specific antigen (PSA) are not satisfied for the resectable PCa due to its low specificity, unclear benefits for reducing PCa deaths and the harms of overdiagnosing indolent disease. Methods: We investigated the performance of uEVEpCAM-CD9 from urine samples of 193 participates ( 112 PCa, 55 BPH and 26 HD) to diagnose the prostate cancer using our laboratory-developed chemiluminescent immunoassay. We applied machine learning to training sets and subsequently evaluated the multivariate diagnostic model based on uEVEpCAM-CD9 in validation sets. Findings: Results showed uEVEpCAM-CD9 were able to distinguish PCa from controls and significant decrease of uEVEpCAM-CD9 were observed after prostatectomy. We further used a training set (N=116) and constructed an exclusive multivariate diagnostic model based on uEVEpCAM-CD9, PSA and other clinical parameters, which showed an enhanced diagnostic sensitivity and specificity and performed excellently to diagnose prostate cancer (AUC = 0.952). When applied to a validation test (N= 77), the model achieved an area under the curve of 0.947. Moreover, this diagnostic model also exhibited a superior diagnostic performance (AUC = 0.917) over PSA (AUC = 0.712) at the PSA gray zone. Interpretation: The multivariate model based on uEVEpCAM-CD9 achieved notable diagnostic performance to diagnose PCa. Funding: This study was funded by National Natural Science Foundation of China Youth Science Foundation Project (81902156) and Zhejiang Provincial Natural Science Foundation of China (LQ21H160016). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: Approval was obtained from the Second Affiliated Hospital of Zhejiang University School of Medicine Ethical Committee before initiating the study, and the requirement for informed consent was waived due to the retrospective nature of this study. All methods were performed in accordance with the relevant guidelines and regulations.