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Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study

BACKGROUND: Aspiration pneumonia (AP), which is a major cause of death in the elderly, does present with typical symptoms in the early stages of onset, thus it is difficult to detect and treat at an early stage. In this study, we identified biomarkers that are useful for the detection of AP and focu...

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Autores principales: Ogura, Kohei, Endo, Maho, Hase, Takashi, Negami, Hitomi, Tsuchiya, Kohsuke, Nishiuchi, Takumi, Suzuki, Takeshi, Ogai, Kazuhiro, Sanada, Hiromi, Okamoto, Shigefumi, Sugama, Junko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996945/
https://www.ncbi.nlm.nih.gov/pubmed/36894881
http://dx.doi.org/10.1186/s12014-023-09398-w
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author Ogura, Kohei
Endo, Maho
Hase, Takashi
Negami, Hitomi
Tsuchiya, Kohsuke
Nishiuchi, Takumi
Suzuki, Takeshi
Ogai, Kazuhiro
Sanada, Hiromi
Okamoto, Shigefumi
Sugama, Junko
author_facet Ogura, Kohei
Endo, Maho
Hase, Takashi
Negami, Hitomi
Tsuchiya, Kohsuke
Nishiuchi, Takumi
Suzuki, Takeshi
Ogai, Kazuhiro
Sanada, Hiromi
Okamoto, Shigefumi
Sugama, Junko
author_sort Ogura, Kohei
collection PubMed
description BACKGROUND: Aspiration pneumonia (AP), which is a major cause of death in the elderly, does present with typical symptoms in the early stages of onset, thus it is difficult to detect and treat at an early stage. In this study, we identified biomarkers that are useful for the detection of AP and focused on salivary proteins, which may be collected non-invasively. Because expectorating saliva is often difficult for elderly people, we collected salivary proteins from the buccal mucosa. METHODS: We collected samples from the buccal mucosa of six patients with AP and six control patients (no AP) in an acute-care hospital. Following protein precipitation using trichloroacetic acid and washing with acetone, the samples were analyzed by liquid chromatography and tandem mass spectrometry (LC–MS/MS). We also determined the levels of cytokines and chemokines in non-precipitated samples from buccal mucosa. RESULTS: Comparative quantitative analysis of LC–MS/MS spectra revealed 55 highly (P values < 0.10) abundant proteins with high FDR confidence (q values < 0.01) and high coverage (> 50%) in the AP group compared with the control group. Among the 55 proteins, the protein abundances of four proteins (protein S100-A7A, eukaryotic translation initiation factor 1, Serpin B4, and peptidoglycan recognition protein 1) in the AP group showed a negative correlation with the time post-onset; these proteins are promising AP biomarker candidates. In addition, the abundance of C-reactive protein (CRP) in oral samples was highly correlated with serum CRP levels, suggesting that oral CRP levels may be used as a surrogate to predict serum CRP in AP patients. A multiplex cytokine/chemokine assay revealed that MCP-1 tended to be low, indicating unresponsiveness of MCP-1 and its downstream immune pathways in AP. CONCLUSION: Our findings suggest that oral salivary proteins, which are obtained non-invasively, can be utilized for the detection of AP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-023-09398-w.
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spelling pubmed-99969452023-03-10 Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study Ogura, Kohei Endo, Maho Hase, Takashi Negami, Hitomi Tsuchiya, Kohsuke Nishiuchi, Takumi Suzuki, Takeshi Ogai, Kazuhiro Sanada, Hiromi Okamoto, Shigefumi Sugama, Junko Clin Proteomics Research BACKGROUND: Aspiration pneumonia (AP), which is a major cause of death in the elderly, does present with typical symptoms in the early stages of onset, thus it is difficult to detect and treat at an early stage. In this study, we identified biomarkers that are useful for the detection of AP and focused on salivary proteins, which may be collected non-invasively. Because expectorating saliva is often difficult for elderly people, we collected salivary proteins from the buccal mucosa. METHODS: We collected samples from the buccal mucosa of six patients with AP and six control patients (no AP) in an acute-care hospital. Following protein precipitation using trichloroacetic acid and washing with acetone, the samples were analyzed by liquid chromatography and tandem mass spectrometry (LC–MS/MS). We also determined the levels of cytokines and chemokines in non-precipitated samples from buccal mucosa. RESULTS: Comparative quantitative analysis of LC–MS/MS spectra revealed 55 highly (P values < 0.10) abundant proteins with high FDR confidence (q values < 0.01) and high coverage (> 50%) in the AP group compared with the control group. Among the 55 proteins, the protein abundances of four proteins (protein S100-A7A, eukaryotic translation initiation factor 1, Serpin B4, and peptidoglycan recognition protein 1) in the AP group showed a negative correlation with the time post-onset; these proteins are promising AP biomarker candidates. In addition, the abundance of C-reactive protein (CRP) in oral samples was highly correlated with serum CRP levels, suggesting that oral CRP levels may be used as a surrogate to predict serum CRP in AP patients. A multiplex cytokine/chemokine assay revealed that MCP-1 tended to be low, indicating unresponsiveness of MCP-1 and its downstream immune pathways in AP. CONCLUSION: Our findings suggest that oral salivary proteins, which are obtained non-invasively, can be utilized for the detection of AP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-023-09398-w. BioMed Central 2023-03-09 /pmc/articles/PMC9996945/ /pubmed/36894881 http://dx.doi.org/10.1186/s12014-023-09398-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ogura, Kohei
Endo, Maho
Hase, Takashi
Negami, Hitomi
Tsuchiya, Kohsuke
Nishiuchi, Takumi
Suzuki, Takeshi
Ogai, Kazuhiro
Sanada, Hiromi
Okamoto, Shigefumi
Sugama, Junko
Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title_full Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title_fullStr Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title_full_unstemmed Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title_short Potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
title_sort potential biomarker proteins for aspiration pneumonia detected by shotgun proteomics using buccal mucosa samples: a cross-sectional case–control study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996945/
https://www.ncbi.nlm.nih.gov/pubmed/36894881
http://dx.doi.org/10.1186/s12014-023-09398-w
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