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Early Detection of NSCLC with scFv Selected against IgM Autoantibody
Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621672/ https://www.ncbi.nlm.nih.gov/pubmed/23585862 http://dx.doi.org/10.1371/journal.pone.0060934 |
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author | Pedchenko, Tetyana Mernaugh, Ray Parekh, Dipti Li, Ming Massion, Pierre P. |
author_facet | Pedchenko, Tetyana Mernaugh, Ray Parekh, Dipti Li, Ming Massion, Pierre P. |
author_sort | Pedchenko, Tetyana |
collection | PubMed |
description | Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to select for recombinant scFvs that specifically bind to lung cancer-associated IgM autoantibodies. We selected for scFv recombinant antibodies reactive with circulating IgM autoantibodies found in the serum of patients with early stage lung adenocarcinoma but not matched controls. Discriminatory performance of 6 selected scFvs was validated in an independent set of serum from stage 1 adenocarcinoma and matching control groups using two independent novel methods developed for this application. The panel of 6 selected scFvs predicted cancer based on seroreactivity value with sensitivity of 0.8 and specificity of 0.87. Receiver Operative Characteristic curve (ROC) for combined 6 scFv has an AUC of 0.88 (95%CI, 0.76–1.0) as determined by fluorometric microvolume assay technology (FMAT) The ROC curve generated using a homogeneous bridging Mesa Scale Discovery (MSD) assay had an AUC of 0.72 (95% CI, 0.59–0.85). The panel of all 6 antibodies demonstrated better discriminative power than any single scFv alone. The scFv panel also demonstrated the association between a high score - based on seroreactivity - with poor survival. Selected scFvs were able to recognize lung cancer associated IgM autoantibodies in patient serum as early as 21 months before the clinical presentation of disease. The panel of antibodies discovered represents a potential unique non-invasive molecular tool to detect an immune response specific to lung adenocarcinoma at an early stage of disease. |
format | Online Article Text |
id | pubmed-3621672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36216722013-04-12 Early Detection of NSCLC with scFv Selected against IgM Autoantibody Pedchenko, Tetyana Mernaugh, Ray Parekh, Dipti Li, Ming Massion, Pierre P. PLoS One Research Article Survival of patients with lung cancer could be significantly prolonged should the disease be diagnosed early. Growing evidence indicates that the immune response in the form of autoantibodies to developing cancer is present before clinical presentation. We used a phage-displayed antibody library to select for recombinant scFvs that specifically bind to lung cancer-associated IgM autoantibodies. We selected for scFv recombinant antibodies reactive with circulating IgM autoantibodies found in the serum of patients with early stage lung adenocarcinoma but not matched controls. Discriminatory performance of 6 selected scFvs was validated in an independent set of serum from stage 1 adenocarcinoma and matching control groups using two independent novel methods developed for this application. The panel of 6 selected scFvs predicted cancer based on seroreactivity value with sensitivity of 0.8 and specificity of 0.87. Receiver Operative Characteristic curve (ROC) for combined 6 scFv has an AUC of 0.88 (95%CI, 0.76–1.0) as determined by fluorometric microvolume assay technology (FMAT) The ROC curve generated using a homogeneous bridging Mesa Scale Discovery (MSD) assay had an AUC of 0.72 (95% CI, 0.59–0.85). The panel of all 6 antibodies demonstrated better discriminative power than any single scFv alone. The scFv panel also demonstrated the association between a high score - based on seroreactivity - with poor survival. Selected scFvs were able to recognize lung cancer associated IgM autoantibodies in patient serum as early as 21 months before the clinical presentation of disease. The panel of antibodies discovered represents a potential unique non-invasive molecular tool to detect an immune response specific to lung adenocarcinoma at an early stage of disease. Public Library of Science 2013-04-09 /pmc/articles/PMC3621672/ /pubmed/23585862 http://dx.doi.org/10.1371/journal.pone.0060934 Text en © 2013 Pedchenko et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pedchenko, Tetyana Mernaugh, Ray Parekh, Dipti Li, Ming Massion, Pierre P. Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title | Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title_full | Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title_fullStr | Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title_full_unstemmed | Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title_short | Early Detection of NSCLC with scFv Selected against IgM Autoantibody |
title_sort | early detection of nsclc with scfv selected against igm autoantibody |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621672/ https://www.ncbi.nlm.nih.gov/pubmed/23585862 http://dx.doi.org/10.1371/journal.pone.0060934 |
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