Circulating extracellular vesicles in serum carry Trop2 marker for prostate cancer liquid biopsy and clinical care

Extracellular vesicles (EVs) are lipid nano-to-micro-sized vesicles increasingly identified as valuable liquid biopsy tools for medical applications. However, the heterogeneity of cargo and the lack of convenient quantification methods to characterize EVs pose challenges in identifying vesicles with specific markers. In this study, we show the isolation, characterization, detection, and quantification of a cancer-specific marker, Trop2, on circulating extracellular vesicles in serum (EV-Trop2). This work combines the unique advantages of our user-friendly isolation method with serum diagnostics to identify high-risk prostate cancer cases and predict recurrence after prostate surgery. To our knowledge, this is the first demonstration to isolate and quantify EV-Trop2 from prostate cancer patient serum to study its analytical validity and potential clinical utility as an EV-based liquid biopsy. Initial study with patient serum samples from three clinical groups: high- risk prostate cancer (n = 22), low-risk prostate cancer (n = 23), and cancer-free groups (n = 21), demonstrates the potential of this approach in distinguishing prostate cancer aggressiveness. We observed significantly different levels of EV-Trop2 expression between the high-risk and low-risk patient groups (p = 0.0015), and between high-risk patient and cancer-free groups (p < 0.0001). Furthermore, employing machine learning algorithms, EV-Trop2 was shown to enhance classifier metrics across the three sample groups, aiding both in risk stratification and predicting recurrence post-prostatectomy. The availability of such tool could have a broad impact across multiple cancers by enabling minimally invasive liquid biopsy sampling.