前列腺病变患者组织和尿液中的代谢组学分析及尿液细胞外囊泡代谢物在前列腺癌中的诊断价值。

Metabolic profiling in tissues and urine of patients with prostatic lesions and the diagnostic value of urine extracellular vesicles metabolites in prostate cancer.

机构信息

Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi'an, China; School of Medicine, Northwest University, Xi'an, China.

Department of Urology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi'an, China.

出版信息

Clin Chim Acta. 2024 Mar 15;556:117845. doi: 10.1016/j.cca.2024.117845. Epub 2024 Feb 23.

DOI:10.1016/j.cca.2024.117845

PMID:38403146

Abstract

BACKGROUND

Prostate cancer (PCa) lacks convenient and highly specific diagnostic markers. Although the value of extracellular vesicles (EV) in oncology is widely recognized, the diagnostic value of EV metabolites requires further exploration. This study aimed to explore the diagnostic value of urine EV (u-EV) metabolomics in PCa.

METHODS

We first detected metabolites in paired tissues cells (cells), tissue EV (t-EVs), u-EVs, and urine samples in cohort 1 (8 PCa vs. 5 benign prostatic hypertrophy, BPH) to prob the feasibility of EV metabolites as diagnostic markers. We then analyzed the value of u-EVs as markers for PCa diagnosis and typing in the expanded sample cohort (60 PCa vs. 40 BPH).

RESULTS

U-EV metabolites were more consistent with those in tissue-derived samples (cells and t-EVs) than those in urine, and more differential metabolites between BPH and PCa were identified in u-EV. Subsequently, we used a random forest model to construct a panel of six metabolites for PCa, which showed an area under the curve (AUC) of 0.833 in training cohort and 0.844 in validation cohort. We also found significantly differentially expressed metabolites between PCa subtypes (Gleason ≤ 7 vs. Gleason > 7 and localized vs. metastasis), demonstrating the value of EV metabolites in PCa typing and prognostic assessment.

CONCLUSION

Metabolomic analysis of u-EVs is a promising source of noninvasive markers for PCa diagnosis.

摘要

背景

前列腺癌（PCa）缺乏便捷且高度特异的诊断标志物。尽管细胞外囊泡（EV）在肿瘤学中的价值已得到广泛认可，但 EV 代谢物的诊断价值仍需进一步探索。本研究旨在探讨尿 EV（u-EV）代谢组学在 PCa 诊断中的价值。

方法

我们首先在队列 1（8 例 PCa 对 5 例良性前列腺增生，BPH）中检测配对组织细胞（cells）、组织 EV（t-EVs）、u-EVs 和尿液样本中的代谢物，以验证 EV 代谢物作为诊断标志物的可行性。然后，我们在扩展样本队列（60 例 PCa 对 40 例 BPH）中分析 u-EVs 作为 PCa 诊断和分型标志物的价值。

结果

u-EV 代谢物与组织来源样本（cells 和 t-EVs）更一致，而与尿液样本差异更大，u-EV 中鉴定出更多的 BPH 和 PCa 之间的差异代谢物。随后，我们使用随机森林模型构建了一个用于 PCa 的 6 种代谢物的面板，在训练队列中 AUC 为 0.833，在验证队列中 AUC 为 0.844。我们还发现 PCa 亚型（Gleason≤7 对 Gleason＞7 和局限性对转移）之间存在明显差异表达的代谢物，表明 EV 代谢物在 PCa 分型和预后评估中的价值。