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  • IgM and IgA augmented autoantibody signatures improve early-stage detection of colorectal cancer prior to nodal and distant spread

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    Nguyen514627-Published.pdf (1.843Mb)
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    Version of Record (VoR)
    Author(s)
    Roney, MSI
    Lanagan, C
    Sheng, YH
    Lawler, K
    Schmidt, C
    Nguyen, NT
    Begun, J
    Kijanka, GS
    Griffith University Author(s)
    Nguyen, Nam-Trung
    Kijanka, Gregor
    Year published
    2021
    Metadata
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    Abstract
    Objectives: Tumor-associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa-associated IgA can aid IgG AAbs in the detection of early-stage colorectal cancer (CRC). Methods: We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex- and age-matched non-cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and ...
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    Objectives: Tumor-associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa-associated IgA can aid IgG AAbs in the detection of early-stage colorectal cancer (CRC). Methods: We developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex- and age-matched non-cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and univariate and multivariate Cox regression analyses were conducted. Results: We identified a panel of 16 multi-isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850–0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884–0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440–0.601) balanced across all CRC stages. Kaplan–Meier analysis revealed that se33-1 (ZNF638) IgG AAbs were associated with reduced 5-year overall survival (log-rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5-year overall survival (log-rank test, P = 0.024). Conclusion: IgM AAbs are associated with early-stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.
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    Journal Title
    Clinical and Translational Immunology
    Volume
    10
    Issue
    9
    DOI
    https://doi.org/10.1002/cti2.1330
    Copyright Statement
    © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Immunology
    Basic pharmacology
    Oncology and carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/408733
    Collection
    • Journal articles

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