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

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 Chu; Peter Mu Hsin Chang; Pei Hung Chang; Chi Ying F. Huang; Cheng Hsu Wang; Yan Shen Shan; Chung Pin Li; Martin Fleisher; L. James Lee

doi:10.1002/advs.202306373

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

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 ReateguiYeh Shiu Chu, Peter Mu Hsin Chang, Pei Hung Chang, Chi Ying F. Huang^*, Cheng Hsu Wang^*, Yan Shen Shan^*, Chung Pin Li^*, Martin Fleisher^*, L. James Lee^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Article number	2306373
Journal	Advanced Science
Volume	11
Issue number	11
DOIs	https://doi.org/10.1002/advs.202306373
State	Published - 20 Mar 2024

Keywords

Glypican 1 mRNA in exosomes and protein in tumor-associated microvesicles as a dual biomarker
PDAC screening and chemotherapy prognosis
immune lipoplex nanoparticle biochip assay
single extracellular vesicle analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/advs.202306373

Cite this

Li, H., Chiang, C. L., Kwak, K. J., Wang, X., Doddi, S., Ramanathan, L. V., Cho, S. M., Hou, Y. C., Cheng, T. S., Mo, X., Chang, Y. S., Chang, H. L., Cheng, W., Tsai, W. N., Nguyen, L. T. H., Pan, J., Ma, Y., Rima, X. Y., Zhang, J., ... Lee, L. J. (2024). Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis. Advanced Science, 11(11), Article 2306373. https://doi.org/10.1002/advs.202306373

@article{a57e19238310491ba9abac1977bee6fa,

title = "Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis",

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.",

keywords = "Glypican 1 mRNA in exosomes and protein in tumor-associated microvesicles as a dual biomarker, PDAC screening and chemotherapy prognosis, immune lipoplex nanoparticle biochip assay, single extracellular vesicle analysis",

author = "Hong Li and Chiang, {Chi Ling} and Kwak, {Kwang Joo} and Xinyu Wang and Sital Doddi and Ramanathan, {Lakshmi V.} and Cho, {Sun M.} and Hou, {Ya Chin} and Cheng, {Tai Shan} and Xiaokui Mo and Chang, {Yueh Shih} and Chang, {Hui Lan} and Weiming Cheng and Tsai, {Wei Ni} and Nguyen, {Luong T.H.} and Junjie Pan and Yifan Ma and Rima, {Xilal Y.} and Jingjing Zhang and Eduardo Reategui and Chu, {Yeh Shiu} and Chang, {Peter Mu Hsin} and Chang, {Pei Hung} and Huang, {Chi Ying F.} and Wang, {Cheng Hsu} and Shan, {Yan Shen} and Li, {Chung Pin} and Martin Fleisher and Lee, {L. James}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.",

year = "2024",

month = mar,

day = "20",

doi = "10.1002/advs.202306373",

language = "English",

volume = "11",

journal = "Advanced Science",

issn = "2198-3844",

publisher = "Wiley-VCH Verlag",

number = "11",

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Li, H, Chiang, CL, Kwak, KJ, Wang, X, Doddi, S, Ramanathan, LV, Cho, SM, Hou, YC, Cheng, TS, Mo, X, Chang, YS, Chang, HL, Cheng, W, Tsai, WN, Nguyen, LTH, Pan, J, Ma, Y, Rima, XY, Zhang, J, Reategui, E, Chu, YS , Chang, PMH, Chang, PH, Huang, CYF, Wang, CH, Shan, YS, Li, CP, Fleisher, M & Lee, LJ 2024, 'Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis', Advanced Science, vol. 11, no. 11, 2306373. https://doi.org/10.1002/advs.202306373

TY - JOUR

T1 - Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis

AU - Li, Hong

AU - Chiang, Chi Ling

AU - Kwak, Kwang Joo

AU - Wang, Xinyu

AU - Doddi, Sital

AU - Ramanathan, Lakshmi V.

AU - Cho, Sun M.

AU - Hou, Ya Chin

AU - Cheng, Tai Shan

AU - Mo, Xiaokui

AU - Chang, Yueh Shih

AU - Chang, Hui Lan

AU - Cheng, Weiming

AU - Tsai, Wei Ni

AU - Nguyen, Luong T.H.

AU - Pan, Junjie

AU - Ma, Yifan

AU - Rima, Xilal Y.

AU - Zhang, Jingjing

AU - Reategui, Eduardo

AU - Chu, Yeh Shiu

AU - Chang, Peter Mu Hsin

AU - Chang, Pei Hung

AU - Huang, Chi Ying F.

AU - Wang, Cheng Hsu

AU - Shan, Yan Shen

AU - Li, Chung Pin

AU - Fleisher, Martin

AU - Lee, L. James

PY - 2024/3/20

Y1 - 2024/3/20

N2 - 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.

AB - 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.

KW - Glypican 1 mRNA in exosomes and protein in tumor-associated microvesicles as a dual biomarker

KW - PDAC screening and chemotherapy prognosis

KW - immune lipoplex nanoparticle biochip assay

KW - single extracellular vesicle analysis

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U2 - 10.1002/advs.202306373

DO - 10.1002/advs.202306373

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AN - SCOPUS:85181893446

SN - 2198-3844

VL - 11

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