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Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung
BACKGROUND: The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relev...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664554/ https://www.ncbi.nlm.nih.gov/pubmed/31357969 http://dx.doi.org/10.1186/s12885-019-5943-3 |
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author | Djureinovic, Dijana Pontén, Victor Landelius, Per Al Sayegh, Sahar Kappert, Kai Kamali-Moghaddam, Masood Micke, Patrick Ståhle, Elisabeth |
author_facet | Djureinovic, Dijana Pontén, Victor Landelius, Per Al Sayegh, Sahar Kappert, Kai Kamali-Moghaddam, Masood Micke, Patrick Ståhle, Elisabeth |
author_sort | Djureinovic, Dijana |
collection | PubMed |
description | BACKGROUND: The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relevance. The aim of this study was to identify and validate novel protein markers in plasma using the highly sensitive DNA-assisted multiplex proximity extension assay (PEA) to discriminate NSCLC from other lung diseases. METHODS: Plasma samples were collected from a total of 343 patients who underwent surgical resection for different lung diseases, including 144 patients with lung adenocarcinoma (LAC), 68 patients with non-malignant lung disease, 83 patients with lung metastasis of colorectal cancers and 48 patients with typical carcinoid. One microliter of plasma was analyzed using PEA, allowing detection and quantification of 92 established cancer related proteins. The concentrations of the plasma proteins were compared between disease groups. RESULTS: The comparison between LAC and benign samples revealed significantly different plasma levels for four proteins; CXCL17, CEACAM5, VEGFR2 and ERBB3 (adjusted p-value < 0.05). A multi-parameter classifier was developed to discriminate between samples from LAC patients and from patients with non-malignant lung conditions. With a bootstrap aggregated decision tree algorithm (TreeBagger), a sensitivity of 93% and specificity of 64% was achieved to detect LAC in this risk population. CONCLUSIONS: By applying the highly sensitive PEA, reliable protein profiles could be determined in microliter amounts of plasma. We further identified proteins that demonstrated different plasma concentration in defined disease groups and developed a signature that holds potential to be included in a screening assay for early lung cancer detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5943-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6664554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66645542019-08-05 Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung Djureinovic, Dijana Pontén, Victor Landelius, Per Al Sayegh, Sahar Kappert, Kai Kamali-Moghaddam, Masood Micke, Patrick Ståhle, Elisabeth BMC Cancer Research Article BACKGROUND: The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relevance. The aim of this study was to identify and validate novel protein markers in plasma using the highly sensitive DNA-assisted multiplex proximity extension assay (PEA) to discriminate NSCLC from other lung diseases. METHODS: Plasma samples were collected from a total of 343 patients who underwent surgical resection for different lung diseases, including 144 patients with lung adenocarcinoma (LAC), 68 patients with non-malignant lung disease, 83 patients with lung metastasis of colorectal cancers and 48 patients with typical carcinoid. One microliter of plasma was analyzed using PEA, allowing detection and quantification of 92 established cancer related proteins. The concentrations of the plasma proteins were compared between disease groups. RESULTS: The comparison between LAC and benign samples revealed significantly different plasma levels for four proteins; CXCL17, CEACAM5, VEGFR2 and ERBB3 (adjusted p-value < 0.05). A multi-parameter classifier was developed to discriminate between samples from LAC patients and from patients with non-malignant lung conditions. With a bootstrap aggregated decision tree algorithm (TreeBagger), a sensitivity of 93% and specificity of 64% was achieved to detect LAC in this risk population. CONCLUSIONS: By applying the highly sensitive PEA, reliable protein profiles could be determined in microliter amounts of plasma. We further identified proteins that demonstrated different plasma concentration in defined disease groups and developed a signature that holds potential to be included in a screening assay for early lung cancer detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5943-3) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-29 /pmc/articles/PMC6664554/ /pubmed/31357969 http://dx.doi.org/10.1186/s12885-019-5943-3 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Djureinovic, Dijana Pontén, Victor Landelius, Per Al Sayegh, Sahar Kappert, Kai Kamali-Moghaddam, Masood Micke, Patrick Ståhle, Elisabeth Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title | Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title_full | Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title_fullStr | Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title_full_unstemmed | Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title_short | Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
title_sort | multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664554/ https://www.ncbi.nlm.nih.gov/pubmed/31357969 http://dx.doi.org/10.1186/s12885-019-5943-3 |
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