An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients

Abstract Conventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (AuSE...

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Main Authors: Luong T. H. Nguyen, Jingjing Zhang, Xilal Y. Rima, Xinyu Wang, Kwang Joo Kwak, Tamio Okimoto, Joseph Amann, Min Jin Yoon, Takehito Shukuya, Chi‐Ling Chiang, Nicole Walters, Yifan Ma, Donald Belcher, Hong Li, Andre F. Palmer, David P. Carbone, L. James Lee, Eduardo Reátegui
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:Journal of Extracellular Vesicles
Online Access:https://doi.org/10.1002/jev2.12258
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author Luong T. H. Nguyen
Jingjing Zhang
Xilal Y. Rima
Xinyu Wang
Kwang Joo Kwak
Tamio Okimoto
Joseph Amann
Min Jin Yoon
Takehito Shukuya
Chi‐Ling Chiang
Nicole Walters
Yifan Ma
Donald Belcher
Hong Li
Andre F. Palmer
David P. Carbone
L. James Lee
Eduardo Reátegui
author_facet Luong T. H. Nguyen
Jingjing Zhang
Xilal Y. Rima
Xinyu Wang
Kwang Joo Kwak
Tamio Okimoto
Joseph Amann
Min Jin Yoon
Takehito Shukuya
Chi‐Ling Chiang
Nicole Walters
Yifan Ma
Donald Belcher
Hong Li
Andre F. Palmer
David P. Carbone
L. James Lee
Eduardo Reátegui
author_sort Luong T. H. Nguyen
collection DOAJ
description Abstract Conventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (AuSERP) as a non‐invasive alternative. With only 20 μl of purified serum, PD‐1/PD‐L1 proteins on the surface of extracellular vesicles (EVs) and EV PD‐1/PD‐L1 messenger RNA (mRNA) cargo were detected at a single‐vesicle resolution and exceeded the sensitivities of their bulk‐analysis conventional counterparts, ELISA and qRT‐PCR, by 1000 times. By testing a cohort of 27 non‐responding and 27 responding NSCLC patients, AuSERP indicated that the single‐EV mRNA biomarkers surpass the single‐EV protein biomarkers in predicting patient responses to immunotherapy. Dual single‐EV PD‐1/PD‐L1 mRNA detection differentiated responders from non‐responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for AuSERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.
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spelling doaj.art-146b93eb927b403f95099c23ef145b702022-12-22T03:21:19ZengWileyJournal of Extracellular Vesicles2001-30782022-09-01119n/an/a10.1002/jev2.12258An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patientsLuong T. H. Nguyen0Jingjing Zhang1Xilal Y. Rima2Xinyu Wang3Kwang Joo Kwak4Tamio Okimoto5Joseph Amann6Min Jin Yoon7Takehito Shukuya8Chi‐Ling Chiang9Nicole Walters10Yifan Ma11Donald Belcher12Hong Li13Andre F. Palmer14David P. Carbone15L. James Lee16Eduardo Reátegui17William G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USASpot Biosystems Ltd. Palo Alto California USAComprehensive Cancer Center The Ohio State University Columbus Ohio USAComprehensive Cancer Center The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAComprehensive Cancer Center The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAComprehensive Cancer Center The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAWilliam G. Lowrie Department of Chemical and Biomolecular Engineering The Ohio State University Columbus Ohio USAAbstract Conventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (AuSERP) as a non‐invasive alternative. With only 20 μl of purified serum, PD‐1/PD‐L1 proteins on the surface of extracellular vesicles (EVs) and EV PD‐1/PD‐L1 messenger RNA (mRNA) cargo were detected at a single‐vesicle resolution and exceeded the sensitivities of their bulk‐analysis conventional counterparts, ELISA and qRT‐PCR, by 1000 times. By testing a cohort of 27 non‐responding and 27 responding NSCLC patients, AuSERP indicated that the single‐EV mRNA biomarkers surpass the single‐EV protein biomarkers in predicting patient responses to immunotherapy. Dual single‐EV PD‐1/PD‐L1 mRNA detection differentiated responders from non‐responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for AuSERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.https://doi.org/10.1002/jev2.12258
spellingShingle Luong T. H. Nguyen
Jingjing Zhang
Xilal Y. Rima
Xinyu Wang
Kwang Joo Kwak
Tamio Okimoto
Joseph Amann
Min Jin Yoon
Takehito Shukuya
Chi‐Ling Chiang
Nicole Walters
Yifan Ma
Donald Belcher
Hong Li
Andre F. Palmer
David P. Carbone
L. James Lee
Eduardo Reátegui
An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
Journal of Extracellular Vesicles
title An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
title_full An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
title_fullStr An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
title_full_unstemmed An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
title_short An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
title_sort immunogold single extracellular vesicular rna and protein auserp biochip to predict responses to immunotherapy in non small cell lung cancer patients
url https://doi.org/10.1002/jev2.12258
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