Introduction: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision. However, the characterization of plasma-derived EVs in prostate cancer patients remains largely unexplored.Methods: We conducted proteomic analyses on EVs isolated from plasma in 27 metastatic castration-resistant prostate cancer (mCRPC) patients. EVs were purified using ultracentrifugation and analyzed via mass spectrometry. Proteomic data were correlated with clinical markers such as serum prostate-specific antigen (PSA) and bone lesion counts. Statistical significance was assessed using Mann–Whitneyt-tests and Spearman correlation.Results: The median age of patients was 74 (range: 44–94) years. At the time of blood collection, the median PSA level was 70 (range: 0.5–1000) ng/mL. All patients had bone metastasis. A total of 5213 proteins were detected, including EV-related proteins (CD9, CD81, CD63, FLOT1, TSG101) and cancer-related proteins (PSMA, B7-H3, PD-L1).Proteomic profiling of plasma EVs revealed a significant correlation between specific EV-derived proteins and clinical prognostic markers. B7-H3, LAT1, and SLC29A1 showed a strong association with serum PSA levels and number of bone lesions, indicating potential for these proteins to serve as biomarkers of disease burden and therapy response.Conclusions: Our findings demonstrate the potential of EV-based proteomics for identifying biomarkers in mCRPC patients. Proteins such as B7-H3 and LAT1 could guide precision oncology approaches, improving patient stratification. Future research incorporating outcomes data and EV subpopulation analysis is needed to establish clinical relevance.
引言：前列腺癌治疗已因靶向疗法而革新，包括PARP抑制剂、检查点免疫疗法和PSMA靶向放射治疗。尽管取得这些进展，精确的患者分层仍面临挑战，目前方法依赖于基因组标记、组织染色和影像学。细胞外囊泡来源蛋白为生物标志物发现提供了一种新型无创替代方案，有望提升治疗精准度。然而，前列腺癌患者血浆来源细胞外囊泡的特征仍很大程度上未被探索。 方法：我们对27例转移性去势抵抗性前列腺癌患者血浆分离的细胞外囊泡进行蛋白质组学分析。采用超速离心法纯化囊泡，并通过质谱技术进行分析。蛋白质组学数据与血清前列腺特异性抗原和骨转移灶数量等临床标志物进行关联分析。使用曼-惠特尼U检验和斯皮尔曼相关性评估统计学意义。 结果：患者中位年龄为74岁（范围：44-94岁）。采血时中位PSA水平为70纳克/毫升（范围：0.5-1000）。所有患者均存在骨转移。共检测到5213种蛋白质，包括细胞外囊泡相关蛋白（CD9、CD81、CD63、FLOT1、TSG101）和癌症相关蛋白（PSMA、B7-H3、PD-L1）。血浆细胞外囊泡蛋白质组学分析显示，特定囊泡来源蛋白与临床预后标志物存在显著相关性。B7-H3、LAT1和SLC29A1与血清PSA水平及骨转移灶数量呈强相关，表明这些蛋白具有作为疾病负荷和治疗反应生物标志物的潜力。 结论：我们的研究结果证明了基于细胞外囊泡的蛋白质组学在识别转移性去势抵抗性前列腺癌患者生物标志物方面的潜力。B7-H3和LAT1等蛋白可指导精准肿瘤学方法，改善患者分层。未来需要结合预后数据和囊泡亚群分析的研究来确立临床相关性。
肿瘤(癌症)患者之家