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Metaproteomic analysis from cervical biopsies and cytologies identifies proteinaceous biomarkers representing both human and microbial species

J. Faktor, T. Henek, L. Hernychova, A. Singh, B. Vojtesek, J. Polom, R. Bhatia, K. Polom, K. Cuschieri, M. Cruickshank, M. Gurumurthy, DR. Goodlett, S. Al Shboul, SK. Samal, T. Hupp, E. Kalampokas, S. Kote

. 2024 ; 278 (-) : 126460. [pub] 20240622

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24018791

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

Citace poskytuje Crossref.org

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$a The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.
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$a Henek, Tomas $u Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53, Brno, Czech Republic
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$a Hernychova, Lenka $u Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53, Brno, Czech Republic
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$a Singh, Ashita $u University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland, UK
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$a Vojtesek, Borek $u Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53, Brno, Czech Republic
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$a Polom, Joanna $u The Academy of Applied Medical and Social Sciences, Lotnicza 2, Elblag, Poland; Department of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI.pl, Medical University of Gdańsk, Marii Skłodowskiej-Curie 3a, 80-210, Gdańsk, Poland
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$a Bhatia, Ramya $u Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53, Brno, Czech Republic
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$a Polom, Karol $u The Academy of Applied Medical and Social Sciences, Lotnicza 2, Elblag, Poland; Gastrointestinal Surgical Oncology Department, Greater Poland Cancer Centre, Garbary 15, Poznan, Poland
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$a Cuschieri, Kate $u Scottish HPV Reference Laboratory, Royal Infirmary of Edinburgh NHS Lothian UK, UK
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$a Cruickshank, Margaret $u Aberdeen Centre for Women's Health Research, University of Aberdeen, Scotland, UK
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$a Gurumurthy, Mahalakshmi $u Aberdeen Royal Infirmary, Foresterhill Road, Aberdeen, UK
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$a Goodlett, David R $u Biochemistry and Microbiology, University of Victoria, Canada
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$a Al Shboul, Sofian $u Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa, 13133, Jordan
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$a Samal, Shailesh Kumar $u Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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$a Kalampokas, Emmanouil $u Unit of Gynaecologic Oncology, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Greece. Electronic address: m.kalampokas@gmail.com
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$a Kote, Sachin $u International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland. Electronic address: sachin.kote@ug.edu.pl
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