Zeng Wenjuan, Zhang Yong, Wang Xinyuan, Wang Shisheng, Lin Tianhai, Su Tao, Jin Youmei, Yuan Yujia, Luo Mengqi, Zhong Yi, Li Li, Zhang Dingkun, Gong Meng, Cheng Jingqiu, Liu Jingping, Liu Shan, Wang Weiya, Yang Lu, Yang Hao
Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics; National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu610041, China.
Sichuan Provincial Engineering Laboratory of Pathology in Clinical Application, West China Hospital, Sichuan University, Chengdu610041, China.
ACS Nano. 2025 Apr 29;19(16):15896-15911. doi: 10.1021/acsnano.5c01564. Epub 2025 Apr 18.
The serum prostate-specific antigen (PSA) testing is widely used for prostate cancer (PCa) screening but suffers from poor specificity, leading to unnecessary biopsies and overtreatment. The significant potential of extracellular vesicles (EVs) in cancer diagnosis has driven the development of efficient methods to isolate and identify EV biomarkers from large-scale clinical samples. Here, we systematically evaluate five commonly used EV isolation techniques through proteomic profiling of plasma-derived EVs, endorsing TiO-based chemical affinity capture as a superior approach for analyzing EVs from complex clinical samples. This method demonstrates exceptional advantages in speed, throughput, reproducibility, and protein coverage. Using this optimized workflow, we analyzed plasma EVs from 80 patients with PCa and benign prostatic hyperplasia (BPH), identifying growth differentiation factor 15 (GDF15) as a compelling biomarker with a predictive power (AUC) of 0.908 for PCa. Extensive validation across independent cohorts comprising 457 samples, including plasma EVs and prostate tissues, confirmed GDF15's ability to distinguish PCa from BPH and stratify PCa stages. Notably, the combination of GDF15 with PSA further enhanced diagnostic efficiency, particularly for patients in the PSA diagnostic gray zone. This study establishes a robust workflow for EV protein analysis in large clinical cohorts and highlights EV-GDF15 as a promising biomarker for noninvasive PCa diagnosis.
血清前列腺特异性抗原（PSA）检测广泛用于前列腺癌（PCa）筛查，但特异性较差，导致不必要的活检和过度治疗。细胞外囊泡（EVs）在癌症诊断中具有巨大潜力，推动了从大规模临床样本中分离和鉴定EV生物标志物的高效方法的发展。在此，我们通过对血浆来源的EVs进行蛋白质组分析，系统评估了五种常用的EV分离技术，认可基于TiO的化学亲和捕获作为分析复杂临床样本中EVs的优越方法。该方法在速度、通量、重现性和蛋白质覆盖方面表现出卓越优势。使用这种优化的工作流程，我们分析了80例PCa患者和良性前列腺增生（BPH）患者的血浆EVs，确定生长分化因子15（GDF15）为一种有说服力的生物标志物，对PCa的预测能力（AUC）为0.908。在包括457个样本（包括血浆EVs和前列腺组织）的独立队列中进行的广泛验证，证实了GDF15区分PCa和BPH以及对PCa进行分期的能力。值得注意 的是，GDF15与PSA联合使用进一步提高了诊断效率，特别是对于PSA诊断灰色区域的患者。本研究建立了一个用于大型临床队列中EV蛋白质分析的强大工作流程，并突出了EV-GDF15作为无创PCa诊断的有前景的生物标志物。
