The Level of a Short Form of Multidrug Resistance-Associated Protein 1 Is Elevated in Plasma Small Extracellular Vesicles Derived From Patients With Pancreatic Ductal Adenocarcinoma

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

The FASEB Journal Pub Date : 2025-07-18 DOI:10.1096/fj.202500874R

Kritisha Bhandari, Madison Lu, Gillian Marshall, Jeng Shi Kong, Chao Xu, Ajay Jain, Ying Huang, Michael A. Hollingsworth, Wei-Qun Ding

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Abstract

Multidrug resistance-associated protein 1 (MRP1) is an ATP-dependent transmembrane efflux pump that confers drug resistance. MRP1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and other malignancies. However, its diagnostic value in cancer has not been explored. The present study examined MRP1 expression in plasma small extracellular vesicles (sEVs) derived from PDAC and colon cancer patients. The human plasma samples were obtained from the NCI-sponsored Cooperative Human Tissue Network, Stephenson Cancer Center, and Oklahoma Blood Institute. sEVs were isolated using double filtration followed by the polymer precipitation method or using ultracentrifugation. Western blotting was performed to evaluate the expression level of MRP1, and proteomics were applied to confirm the detection of a short form of MRP1 in plasma sEVs. A short form of MRP1, representing the region between QCRL-1 and C-terminus domains of the protein, was identified in plasma sEVs, and its level was significantly elevated in plasma sEVs derived from patients with early- and late-stage PDAC, compared with matched healthy subjects (n = 34 for each group). The level of the short form of MRP1 was also elevated in plasma sEVs derived from patients with colon cancer (n = 44) but not in those derived from patients with breast cancer (n = 15). The levels of the short form of MRP1 in plasma sEVs were not related to the chemotherapy status of the patients. We thus conclude that a short form of MRP1 is identified in plasma sEVs and its expression level is significantly elevated in patients with early-stage and late-stage PDAC, irrespective of their treatment status.

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胰腺导管腺癌患者血浆小细胞外囊泡中多药耐药相关蛋白1的短形式水平升高

多药耐药相关蛋白1 （MRP1）是一种atp依赖性跨膜外排泵，可产生耐药性。MRP1在胰腺导管腺癌（PDAC）和其他恶性肿瘤中过表达。然而，其在癌症诊断中的价值尚未得到探讨。本研究检测了PDAC和结肠癌患者血浆小细胞外囊泡（sev）中MRP1的表达。人类血浆样本来自nci赞助的合作人体组织网络、斯蒂芬森癌症中心和俄克拉何马州血液研究所。sev的分离采用双重过滤+聚合物沉淀法或超离心法。Western blotting检测MRP1的表达水平，蛋白质组学检测血浆sev中MRP1的短表达形式。在血浆sev中发现了MRP1的一种简短形式，代表了该蛋白的QCRL-1和c端结构域之间的区域，与匹配的健康受试者相比，早期和晚期PDAC患者的血浆sev中MRP1的水平显著升高（每组n = 34）。在结肠癌患者（n = 44）的血浆sev中，MRP1短形式的水平也升高，但在乳腺癌患者（n = 15）的血浆sev中没有升高。血浆sev中MRP1短形式的水平与患者的化疗状态无关。因此，我们得出结论，在血浆sev中发现了一种短形式的MRP1，其表达水平在早期和晚期PDAC患者中显著升高，无论其治疗状态如何。

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来源期刊

The FASEB Journal 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

6243

审稿时长

3 months

期刊介绍： The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.