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

被引:20
作者
Li, Hong [1 ]
Chiang, Chi-Ling [1 ]
Kwak, Kwang Joo [2 ]
Wang, Xinyu [1 ]
Doddi, Sital [3 ]
Ramanathan, Lakshmi V. [3 ]
Cho, Sun M. [3 ]
Hou, Ya-Chin [4 ,5 ]
Cheng, Tai-Shan [6 ]
Mo, Xiaokui [7 ]
Chang, Yueh-Shih [8 ,9 ,10 ]
Chang, Hui-Lan [11 ,12 ,13 ,14 ]
Cheng, Weiming [6 ]
Tsai, Wei-Ni [6 ]
Nguyen, Luong T. H. [1 ]
Pan, Junjie [1 ]
Ma, Yifan [15 ]
Rima, Xilal Y. [1 ]
Zhang, Jingjing [1 ]
Reategui, Eduardo [1 ]
Chu, Yeh-Shiu [16 ]
Chang, Peter Mu-Hsin [6 ,14 ,17 ]
Chang, Pei-Hung [8 ,9 ]
Huang, Chi-Ying F. [6 ]
Wang, Cheng-Hsu [9 ]
Shan, Yan-Shen [4 ,5 ]
Li, Chung-Pin [11 ,12 ,13 ,14 ]
Fleisher, Martin [3 ]
Lee, L. James [1 ,6 ]
机构
[1] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA
[2] Spot Biosyst Ltd, Columbus, OH 43212 USA
[3] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA
[4] Natl Cheng Kung Univ, Inst Clin Med, Coll Med, Tainan 70101, Taiwan
[5] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med Coll, Div Gen Surg,Dept Surg, Tainan 70101, Taiwan
[6] Natl Yang Ming Chiao Tung Univ, Inst Biopharmaceut Sci, Taipei 11221, Taiwan
[7] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA
[8] Chang Gung Univ, Coll Med, Sch Tradit Chinese Med, Taoyuan 33302, Taiwan
[9] Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Keelung 20401, Taiwan
[10] Natl Yang Ming Chiao Tung Univ, Inst Clin Med, Taipei 11221, Taiwan
[11] Taipei Vet Gen Hosp, Dept Med, Div Gastroenterol & Hepatol, Taipei 11217, Taiwan
[12] Taipei Vet Gen Hosp, Ctr Canc, Taipei 11217, Taiwan
[13] Taipei Vet Gen Hosp, Dept Med Educ, Div Clin Skills Training, Taipei 11217, Taiwan
[14] Natl Yang Ming Chiao Tung Univ, Coll Med, Sch Med, Taipei 11221, Taiwan
[15] Ohio State Univ, Dept Biomed Engn, Columbus, OH 43210 USA
[16] Natl Yang Ming Chiao Tung Univ, Brain Res Ctr, Taipei 11221, Taiwan
[17] Taipei Vet Gen Hosp, Dept Oncol, Taipei 11217, Taiwan
基金
美国国家卫生研究院;
关键词
Glypican 1 mRNA in exosomes and protein in tumor-associated microvesicles as a dual biomarker; immune lipoplex nanoparticle biochip assay; PDAC screening and chemotherapy prognosis; single extracellular vesicle analysis; CIRCULATING EXOSOMES; SHEDDING LIGHT; SERUM CA19-9; VESICLES; MICROVESICLES; EXPRESSION; CD63; BIOMARKER; MICRORNA; BIOLOGY;
D O I
10.1002/advs.202306373
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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. Detecting pancreatic duct adenocarcinoma (PDAC) is challenging. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings show that combined glypican 1 (GPC1) mRNA expression in exosomes and GPC1 membrane protein expression in tumor associated microvesicles can effectively discriminated PDAC cases from benign pancreatic diseases and healthy donors. Lower vesicular GPC1 expressions before chemotherapy correlate significantly with prolonged overall survival.image
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页数:19
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