Arafa Ali T, Ludwig Megan, Tuncer Onur, Kollitz Lily, Gustafson Ava, Boytim Ella, Luo Christine, Sabal Barbara, Steinberger Daniel, Zhao Yingchun, Dehm Scott M, Cayci Zuzan, Hwang Justin, Villalta Peter W, Antonarakis Emmanuel S, Drake Justin M
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2024 Dec 21;16(24):4261. doi: 10.3390/cancers16244261.
: 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. : 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-Whitney -tests and Spearman correlation. : 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. : 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.
靶向治疗彻底改变了前列腺癌的治疗方式，其中包括聚（ADP - 核糖）聚合酶（PARP）抑制剂、检查点免疫疗法和前列腺特异性膜抗原（PSMA）靶向放疗。尽管有这些进展，但准确的患者分层仍然是一项挑战，目前的方法依赖于基因组标记、组织染色和成像。细胞外囊泡（EV）衍生的蛋白质为生物标志物发现提供了一种新的非侵入性替代方法，有望提高治疗精度。然而，前列腺癌患者血浆来源的EV的特征在很大程度上仍未得到探索。
我们对27例转移性去势抵抗性前列腺癌（mCRPC）患者血浆中分离出的EV进行了蛋白质组学分析。使用超速离心法纯化EV，并通过质谱分析。蛋白质组学数据与临床标志物如血清前列腺特异性抗原（PSA）和骨病变计数相关联。使用曼 - 惠特尼检验和斯皮尔曼相关性评估统计学意义。
患者的中位年龄为74岁（范围：44 - 94岁）。在采血时，中位PSA水平为70 ng/mL（范围：0.5 - 1000 ng/mL）。所有患者均有骨转移。共检测到5213种蛋白质，包括EV相关蛋白（CD9、CD81、CD63、FLOT1、TSG101）和癌症相关蛋白（PSMA、B7 - H3、PD - L1）。血浆EV的蛋白质组学分析揭示了特定EV衍生蛋白与临床预后标志物之间的显著相关性。B7 - H3、LAT1和SLC29A1与血清PSA水平和骨病变数量显示出强烈关联，表明这些蛋白质有可能作为疾病负担和治疗反应的生物标志物。
我们的研究结果证明了基于EV的蛋白质组学在识别mCRPC患者生物标志物方面的潜力。诸如B7 - H3和LAT1等蛋白质可以指导精准肿瘤学方法，改善患者分层。需要纳入结局数据和EV亚群分析的未来研究来确定临床相关性。
