High-throughput single-EV liquid biopsy: Rapid, simultaneous, and multiplexed detection of nucleic acids, proteins, and their combinations
MicroRNAs (miRNAs), mRNA, and proteins in/on extracellular vesicles (EVs) represent potential cancer biomarkers. Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we i...
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| Veröffentlicht in: | Science advances 2020-11, Vol.6 (47), Article 1204 |
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| creator | Zhou, Jian Wu, Zuoren Hu, Jie Yang, Dawei Chen, Xiaoyan Wang, Qin Liu, Jie Dou, Maosen Peng, Wenjun Wu, Yuanyuan Wang, Wenhao Xie, Chenjian Wang, Ming Song, Yuanlin Zeng, Hengshan Bai, Chunxue |
| description | MicroRNAs (miRNAs), mRNA, and proteins in/on extracellular vesicles (EVs) represent potential cancer biomarkers. Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we introduced a High-throughput Nano-bio Chip Integrated System for Liquid Biopsy (HNCIB) system for simultaneous detection of proteins and mRNA/miRNA in a single EV. Validated through systematic control experiments, HNCIB showed high reliability, sensitivity, and specificity. In a panel of 34 patients with lung adenocarcinoma (LUAD) and 35 healthy donors, HNCIB detected an up-regulated expression of programmed death-ligand 1 mRNA and protein and miR-21 in EVs derived from patients with LUAD compared to those from healthy donors. HNCIB has low sample requirement (similar to 90 mu l), fast assay time (similar to 6 hours), and high throughput (up to 384 samples per assay) and would have great potential in the study of EVs and their clinical applications. |
| doi_str_mv | 10.1126/sciadv.abc1204 |
| format | Article |
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Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we introduced a High-throughput Nano-bio Chip Integrated System for Liquid Biopsy (HNCIB) system for simultaneous detection of proteins and mRNA/miRNA in a single EV. Validated through systematic control experiments, HNCIB showed high reliability, sensitivity, and specificity. In a panel of 34 patients with lung adenocarcinoma (LUAD) and 35 healthy donors, HNCIB detected an up-regulated expression of programmed death-ligand 1 mRNA and protein and miR-21 in EVs derived from patients with LUAD compared to those from healthy donors. HNCIB has low sample requirement (similar to 90 mu l), fast assay time (similar to 6 hours), and high throughput (up to 384 samples per assay) and would have great potential in the study of EVs and their clinical applications.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abc1204</identifier><identifier>PMID: 33219024</identifier><language>eng</language><publisher>WASHINGTON: Amer Assoc Advancement Science</publisher><subject>Adenocarcinoma of Lung - diagnosis ; Adenocarcinoma of Lung - genetics ; Cancer ; Extracellular Vesicles - metabolism ; Humans ; Life Sciences ; Liquid Biopsy ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Molecular Biology ; Multidisciplinary Sciences ; Reproducibility of Results ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; SciAdv r-articles ; Science & Technology ; Science & Technology - Other Topics</subject><ispartof>Science advances, 2020-11, Vol.6 (47), Article 1204</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>74</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000592173500013</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c390t-d26af79eaeb31c0fd97633b591e24c07b6e2f0419a4597072c47d2fd700ca4573</citedby><cites>FETCH-LOGICAL-c390t-d26af79eaeb31c0fd97633b591e24c07b6e2f0419a4597072c47d2fd700ca4573</cites><orcidid>0000-0002-8928-143X ; 0000-0003-4736-9457 ; 0000-0001-6262-1513 ; 0000-0002-1825-491X ; 0000-0002-6836-7007 ; 0000-0001-5798-3130 ; 0000-0001-9624-8673</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679165/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679165/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2115,27929,27930,28253,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33219024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Jian</creatorcontrib><creatorcontrib>Wu, Zuoren</creatorcontrib><creatorcontrib>Hu, Jie</creatorcontrib><creatorcontrib>Yang, Dawei</creatorcontrib><creatorcontrib>Chen, Xiaoyan</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Dou, Maosen</creatorcontrib><creatorcontrib>Peng, Wenjun</creatorcontrib><creatorcontrib>Wu, Yuanyuan</creatorcontrib><creatorcontrib>Wang, Wenhao</creatorcontrib><creatorcontrib>Xie, Chenjian</creatorcontrib><creatorcontrib>Wang, Ming</creatorcontrib><creatorcontrib>Song, Yuanlin</creatorcontrib><creatorcontrib>Zeng, Hengshan</creatorcontrib><creatorcontrib>Bai, Chunxue</creatorcontrib><title>High-throughput single-EV liquid biopsy: Rapid, simultaneous, and multiplexed detection of nucleic acids, proteins, and their combinations</title><title>Science advances</title><addtitle>SCI ADV</addtitle><addtitle>Sci Adv</addtitle><description>MicroRNAs (miRNAs), mRNA, and proteins in/on extracellular vesicles (EVs) represent potential cancer biomarkers. Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we introduced a High-throughput Nano-bio Chip Integrated System for Liquid Biopsy (HNCIB) system for simultaneous detection of proteins and mRNA/miRNA in a single EV. Validated through systematic control experiments, HNCIB showed high reliability, sensitivity, and specificity. In a panel of 34 patients with lung adenocarcinoma (LUAD) and 35 healthy donors, HNCIB detected an up-regulated expression of programmed death-ligand 1 mRNA and protein and miR-21 in EVs derived from patients with LUAD compared to those from healthy donors. 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Wu, Zuoren ; Hu, Jie ; Yang, Dawei ; Chen, Xiaoyan ; Wang, Qin ; Liu, Jie ; Dou, Maosen ; Peng, Wenjun ; Wu, Yuanyuan ; Wang, Wenhao ; Xie, Chenjian ; Wang, Ming ; Song, Yuanlin ; Zeng, Hengshan ; Bai, Chunxue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-d26af79eaeb31c0fd97633b591e24c07b6e2f0419a4597072c47d2fd700ca4573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma of Lung - diagnosis</topic><topic>Adenocarcinoma of Lung - genetics</topic><topic>Cancer</topic><topic>Extracellular Vesicles - metabolism</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Liquid Biopsy</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Molecular Biology</topic><topic>Multidisciplinary Sciences</topic><topic>Reproducibility of Results</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>SciAdv r-articles</topic><topic>Science & Technology</topic><topic>Science & Technology - Other Topics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Jian</creatorcontrib><creatorcontrib>Wu, Zuoren</creatorcontrib><creatorcontrib>Hu, Jie</creatorcontrib><creatorcontrib>Yang, Dawei</creatorcontrib><creatorcontrib>Chen, Xiaoyan</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Dou, Maosen</creatorcontrib><creatorcontrib>Peng, Wenjun</creatorcontrib><creatorcontrib>Wu, Yuanyuan</creatorcontrib><creatorcontrib>Wang, Wenhao</creatorcontrib><creatorcontrib>Xie, Chenjian</creatorcontrib><creatorcontrib>Wang, Ming</creatorcontrib><creatorcontrib>Song, Yuanlin</creatorcontrib><creatorcontrib>Zeng, Hengshan</creatorcontrib><creatorcontrib>Bai, Chunxue</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Jian</au><au>Wu, Zuoren</au><au>Hu, Jie</au><au>Yang, Dawei</au><au>Chen, Xiaoyan</au><au>Wang, Qin</au><au>Liu, Jie</au><au>Dou, Maosen</au><au>Peng, Wenjun</au><au>Wu, Yuanyuan</au><au>Wang, Wenhao</au><au>Xie, Chenjian</au><au>Wang, Ming</au><au>Song, Yuanlin</au><au>Zeng, Hengshan</au><au>Bai, Chunxue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-throughput single-EV liquid biopsy: Rapid, simultaneous, and multiplexed detection of nucleic acids, proteins, and their combinations</atitle><jtitle>Science advances</jtitle><stitle>SCI ADV</stitle><addtitle>Sci Adv</addtitle><date>2020-11-20</date><risdate>2020</risdate><volume>6</volume><issue>47</issue><artnum>1204</artnum><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>MicroRNAs (miRNAs), mRNA, and proteins in/on extracellular vesicles (EVs) represent potential cancer biomarkers. Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we introduced a High-throughput Nano-bio Chip Integrated System for Liquid Biopsy (HNCIB) system for simultaneous detection of proteins and mRNA/miRNA in a single EV. Validated through systematic control experiments, HNCIB showed high reliability, sensitivity, and specificity. In a panel of 34 patients with lung adenocarcinoma (LUAD) and 35 healthy donors, HNCIB detected an up-regulated expression of programmed death-ligand 1 mRNA and protein and miR-21 in EVs derived from patients with LUAD compared to those from healthy donors. HNCIB has low sample requirement (similar to 90 mu l), fast assay time (similar to 6 hours), and high throughput (up to 384 samples per assay) and would have great potential in the study of EVs and their clinical applications.</abstract><cop>WASHINGTON</cop><pub>Amer Assoc Advancement Science</pub><pmid>33219024</pmid><doi>10.1126/sciadv.abc1204</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8928-143X</orcidid><orcidid>https://orcid.org/0000-0003-4736-9457</orcidid><orcidid>https://orcid.org/0000-0001-6262-1513</orcidid><orcidid>https://orcid.org/0000-0002-1825-491X</orcidid><orcidid>https://orcid.org/0000-0002-6836-7007</orcidid><orcidid>https://orcid.org/0000-0001-5798-3130</orcidid><orcidid>https://orcid.org/0000-0001-9624-8673</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma of Lung - diagnosis Adenocarcinoma of Lung - genetics Cancer Extracellular Vesicles - metabolism Humans Life Sciences Liquid Biopsy Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - metabolism MicroRNAs - genetics MicroRNAs - metabolism Molecular Biology Multidisciplinary Sciences Reproducibility of Results RNA, Messenger - genetics RNA, Messenger - metabolism SciAdv r-articles Science & Technology Science & Technology - Other Topics |
| title | High-throughput single-EV liquid biopsy: Rapid, simultaneous, and multiplexed detection of nucleic acids, proteins, and their combinations |
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