Development of a Multiplex Autoantibody Test for Detection of Lung Cancer

Lung cancer is the leading cause of cancer-related deaths for both men and women. Early diagnosis of lung cancer has a 5-year survival rate of 48.8%, however, nearly 35% of stage I patients relapses after surgical resection, thus portending a poor prognosis. Therefore, detecting lung cancer in early...

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Main Authors:	Jia, Jing, Wang, Wenzhe, Meng, Wen, Ding, Mingjian, Ma, Shenglin, Wang, Xiaoju
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995760/

id	pubmed-3995760
recordtype	oai_dc
spelling	pubmed-39957602014-04-25 Development of a Multiplex Autoantibody Test for Detection of Lung Cancer Jia, Jing Wang, Wenzhe Meng, Wen Ding, Mingjian Ma, Shenglin Wang, Xiaoju Research Article Lung cancer is the leading cause of cancer-related deaths for both men and women. Early diagnosis of lung cancer has a 5-year survival rate of 48.8%, however, nearly 35% of stage I patients relapses after surgical resection, thus portending a poor prognosis. Therefore, detecting lung cancer in early stage and further identifying the high-risk patients would allow the opportunity to provide adjuvant therapy and possibly increase survival. There is considerable evidence that the immune system produces an autoantibody response to neoplastic cells. The detection of such autoantibodies has been shown to have diagnostic and prognostic value. Here we took advantage of the high-throughput Luminex technique to multiplex a total of 14 tumor-associated autoantigens to detect the autoantibody from the patients sera. The 14 antigens were expressed by in vitro transcription/translation system with HaloTag at N-terminus. The fusion proteins were then covalently immobilized onto the Luminex microspheres conjugated by the halo-link ligand, thus eliminating the protein purification procedure. Sera samples from cancer patients and healthy controls were interacted with the microsphere-antigen complex to measure the autoantibodies. We have developed a quick multiplex detection system for measuring autoantibody signature from patient sera with minimal cross-reaction. A panel of seven autoantibody biomarkers has generated an AUC>80% in distinguishing the lung cancers from healthy controls. This study is the first report by combining Luminex platform and HaloTag technology to detect humoral immune response in cancer patients. Due to the flexibility of the Luminex technology, this approach can be applied to others conditions such as infectious, neurological, and metabolic diseases. One can envision that this multiplex Luminex system as well as the panel of seven biomarkers could be used to screen the high-risk population with subsequent CT test based on the blood test result. Public Library of Science 2014-04-22 /pmc/articles/PMC3995760/ /pubmed/24755629 http://dx.doi.org/10.1371/journal.pone.0095444 Text en © 2014 Jia 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Jia, Jing Wang, Wenzhe Meng, Wen Ding, Mingjian Ma, Shenglin Wang, Xiaoju
spellingShingle	Jia, Jing Wang, Wenzhe Meng, Wen Ding, Mingjian Ma, Shenglin Wang, Xiaoju Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
author_facet	Jia, Jing Wang, Wenzhe Meng, Wen Ding, Mingjian Ma, Shenglin Wang, Xiaoju
author_sort	Jia, Jing
title	Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
title_short	Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
title_full	Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
title_fullStr	Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
title_full_unstemmed	Development of a Multiplex Autoantibody Test for Detection of Lung Cancer
title_sort	development of a multiplex autoantibody test for detection of lung cancer
description	Lung cancer is the leading cause of cancer-related deaths for both men and women. Early diagnosis of lung cancer has a 5-year survival rate of 48.8%, however, nearly 35% of stage I patients relapses after surgical resection, thus portending a poor prognosis. Therefore, detecting lung cancer in early stage and further identifying the high-risk patients would allow the opportunity to provide adjuvant therapy and possibly increase survival. There is considerable evidence that the immune system produces an autoantibody response to neoplastic cells. The detection of such autoantibodies has been shown to have diagnostic and prognostic value. Here we took advantage of the high-throughput Luminex technique to multiplex a total of 14 tumor-associated autoantigens to detect the autoantibody from the patients sera. The 14 antigens were expressed by in vitro transcription/translation system with HaloTag at N-terminus. The fusion proteins were then covalently immobilized onto the Luminex microspheres conjugated by the halo-link ligand, thus eliminating the protein purification procedure. Sera samples from cancer patients and healthy controls were interacted with the microsphere-antigen complex to measure the autoantibodies. We have developed a quick multiplex detection system for measuring autoantibody signature from patient sera with minimal cross-reaction. A panel of seven autoantibody biomarkers has generated an AUC>80% in distinguishing the lung cancers from healthy controls. This study is the first report by combining Luminex platform and HaloTag technology to detect humoral immune response in cancer patients. Due to the flexibility of the Luminex technology, this approach can be applied to others conditions such as infectious, neurological, and metabolic diseases. One can envision that this multiplex Luminex system as well as the panel of seven biomarkers could be used to screen the high-risk population with subsequent CT test based on the blood test result.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995760/
_version_	1612080967851180032

Development of a Multiplex Autoantibody Test for Detection of Lung Cancer

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