Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis

磷脂酰肌醇蛋白聚糖 1 mRNA 和蛋白质的细胞外囊泡分析对胰腺癌诊断和预后的意义

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作者:Hong Li, Chi-Ling Chiang, Kwang Joo Kwak, Xinyu Wang, Sital Doddi, Lakshmi V Ramanathan, Sun M Cho, Ya-Chin Hou, Tai-Shan Cheng, Xiaokui Mo, Yueh-Shih Chang, Hui-Lan Chang, Weiming Cheng, Wei-Ni Tsai, Luong T H Nguyen, Junjie Pan, Yifan Ma, Xilal Y Rima, Jingjing Zhang, Eduardo Reategui, Yeh-Shiu Ch

Abstract

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

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