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Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum
MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising st...
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Published in: | Nature communications 2021-06, Vol.12 (1), p.3515-12, Article 3515 |
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description | MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.
miRNA profiling from patient blood can be used for cancer diagnosis. Here the authors present an electro-optical nanopore sensing platform which allows sensitive and specific miRNA detection directly in human serum and apply to monitoring of miR-141-3p and miR-375-3p in different stage of prostate cancer. |
doi_str_mv | 10.1038/s41467-021-23497-y |
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miRNA profiling from patient blood can be used for cancer diagnosis. Here the authors present an electro-optical nanopore sensing platform which allows sensitive and specific miRNA detection directly in human serum and apply to monitoring of miR-141-3p and miR-375-3p in different stage of prostate cancer.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-021-23497-y</identifier><identifier>PMID: 34112774</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>140/125 ; 631/337/384/331 ; 631/57/2265 ; 631/67/1857 ; 639/925/350 ; 9/10 ; Biomarkers ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Blood ; Blood circulation ; Body fluids ; Circulating MicroRNA - analysis ; Circulating MicroRNA - blood ; Circulating MicroRNA - genetics ; Diagnosis ; Diagnostic systems ; Early Detection of Cancer - instrumentation ; Early Detection of Cancer - methods ; Fluorescence ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic - genetics ; Humanities and Social Sciences ; Humans ; Liquid Biopsy ; Male ; Medical diagnosis ; MicroRNAs ; MicroRNAs - analysis ; MicroRNAs - blood ; MicroRNAs - genetics ; miRNA ; Monitoring ; multidisciplinary ; Multiplexing ; Nanopores ; Post-transcription ; Prostate cancer ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Real-Time Polymerase Chain Reaction ; Remission ; Ribonucleic acid ; RNA ; Science ; Science (multidisciplinary) ; Selectivity ; Sensitivity and Specificity ; Single Molecule Imaging - methods ; Telemedicine</subject><ispartof>Nature communications, 2021-06, Vol.12 (1), p.3515-12, Article 3515</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c606t-fc2fd858f4ff654d80d6b9477583655090d8b37026873357d0bcbd327da43b613</citedby><cites>FETCH-LOGICAL-c606t-fc2fd858f4ff654d80d6b9477583655090d8b37026873357d0bcbd327da43b613</cites><orcidid>0000-0002-7533-0552 ; 0000-0001-5870-8659 ; 0000-0003-1419-1381 ; 0000-0002-7619-5962 ; 0000-0001-8288-8012 ; 0000-0002-3358-9638 ; 0000-0002-7815-6406</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2539746060/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2539746060?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34112774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Shenglin</creatorcontrib><creatorcontrib>Pataillot-Meakin, Thomas</creatorcontrib><creatorcontrib>Shibakawa, Akifumi</creatorcontrib><creatorcontrib>Ren, Ren</creatorcontrib><creatorcontrib>Bevan, Charlotte L.</creatorcontrib><creatorcontrib>Ladame, Sylvain</creatorcontrib><creatorcontrib>Ivanov, Aleksandar P.</creatorcontrib><creatorcontrib>Edel, Joshua B.</creatorcontrib><title>Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.
miRNA profiling from patient blood can be used for cancer diagnosis. 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Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.
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subjects | 140/125 631/337/384/331 631/57/2265 631/67/1857 639/925/350 9/10 Biomarkers Biomarkers, Tumor - analysis Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Blood Blood circulation Body fluids Circulating MicroRNA - analysis Circulating MicroRNA - blood Circulating MicroRNA - genetics Diagnosis Diagnostic systems Early Detection of Cancer - instrumentation Early Detection of Cancer - methods Fluorescence Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic - genetics Humanities and Social Sciences Humans Liquid Biopsy Male Medical diagnosis MicroRNAs MicroRNAs - analysis MicroRNAs - blood MicroRNAs - genetics miRNA Monitoring multidisciplinary Multiplexing Nanopores Post-transcription Prostate cancer Prostatic Neoplasms - blood Prostatic Neoplasms - diagnosis Prostatic Neoplasms - genetics Real-Time Polymerase Chain Reaction Remission Ribonucleic acid RNA Science Science (multidisciplinary) Selectivity Sensitivity and Specificity Single Molecule Imaging - methods Telemedicine |
title | Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum |
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