BARD1 serum autoantibodies for the detection of lung cancer

Maxim Pilyugin, Pascaline Descloux, Pierre Alain André, Viktoria Laszlo, Balazs Dome, Balazs Hegedus, Sylvain Sardy, Samuel Janes, Andrea Bianco, Geoffrey J. Laurent, Irmgard Irminger-Finger

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: Currently the screening for lung cancer for risk groups is based on Computed Tomography (CT) or low dose CT (LDCT); however, the lung cancer death rate has not decreased significantly with people undergoing LDCT. We aimed to develop a simple reliable blood test for early detection of all types of lung cancer based on the immunogenicity of aberrant forms of BARD1 that are specifically upregulated in lung cancer. Methods: ELISA assays were performed with a panel of BARD1 epitopes to detect serum levels of antibodies against BARD1 epitopes. We tested 194 blood samples from healthy donors and lung cancer patients with a panel of 40 BARD1 antigens. Using fitted Lasso logistic regression we determined the optimal combination of BARD1 antigens to be used in ELISA for discriminating lung cancer from healthy controls. Random selection of samples for training sets or validations sets was applied to validate the accuracy of our test. Results: Fitted Lasso logistic regression models predict high accuracy of the BARD1 autoimmune antibody test with an AUC = 0.96. Validation in independent samples provided and AUC = 0.86 and identical AUCs were obtained for combined stages 1–3 and late stage 4 lung cancers. The BARD1 antibody test is highly specific for lung cancer and not breast or ovarian cancer. Conclusion: The BARD1 lung cancer test shows higher sensitivity and specificity than previously published blood tests for lung cancer detection and/or diagnosis or CT scans, and it could detect all types and all stages of lung cancer. This BARD1 lung cancer test could therefore be further developed as i) screening test for early detection of lung cancers in high-risk groups, and ii) diagnostic aid in complementing CT scan.

Original languageEnglish
Article numbere0182356
JournalPLoS One
Volume12
Issue number8
DOIs
Publication statusPublished - 7 Aug 2017

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autoantibodies
lung neoplasms
blood serum
Autoantibodies
Tomography
Lung Neoplasms
Blood
Serum
Logistics
Antibodies
Epitopes
Screening
Antigens
computed tomography
Assays
Area Under Curve
hematologic tests
risk groups
Logistic Models
Hematologic Tests

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Pilyugin, M., Descloux, P., André, P. A., Laszlo, V., Dome, B., Hegedus, B., ... Irminger-Finger, I. (2017). BARD1 serum autoantibodies for the detection of lung cancer. PLoS One, 12(8), [e0182356]. https://doi.org/10.1371/journal.pone.0182356
Pilyugin, Maxim ; Descloux, Pascaline ; André, Pierre Alain ; Laszlo, Viktoria ; Dome, Balazs ; Hegedus, Balazs ; Sardy, Sylvain ; Janes, Samuel ; Bianco, Andrea ; Laurent, Geoffrey J. ; Irminger-Finger, Irmgard. / BARD1 serum autoantibodies for the detection of lung cancer. In: PLoS One. 2017 ; Vol. 12, No. 8.
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Pilyugin, M, Descloux, P, André, PA, Laszlo, V, Dome, B, Hegedus, B, Sardy, S, Janes, S, Bianco, A, Laurent, GJ & Irminger-Finger, I 2017, 'BARD1 serum autoantibodies for the detection of lung cancer' PLoS One, vol. 12, no. 8, e0182356. https://doi.org/10.1371/journal.pone.0182356

BARD1 serum autoantibodies for the detection of lung cancer. / Pilyugin, Maxim; Descloux, Pascaline; André, Pierre Alain; Laszlo, Viktoria; Dome, Balazs; Hegedus, Balazs; Sardy, Sylvain; Janes, Samuel; Bianco, Andrea; Laurent, Geoffrey J.; Irminger-Finger, Irmgard.

In: PLoS One, Vol. 12, No. 8, e0182356, 07.08.2017.

Research output: Contribution to journalArticle

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AU - Pilyugin, Maxim

AU - Descloux, Pascaline

AU - André, Pierre Alain

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AU - Hegedus, Balazs

AU - Sardy, Sylvain

AU - Janes, Samuel

AU - Bianco, Andrea

AU - Laurent, Geoffrey J.

AU - Irminger-Finger, Irmgard

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N2 - Purpose: Currently the screening for lung cancer for risk groups is based on Computed Tomography (CT) or low dose CT (LDCT); however, the lung cancer death rate has not decreased significantly with people undergoing LDCT. We aimed to develop a simple reliable blood test for early detection of all types of lung cancer based on the immunogenicity of aberrant forms of BARD1 that are specifically upregulated in lung cancer. Methods: ELISA assays were performed with a panel of BARD1 epitopes to detect serum levels of antibodies against BARD1 epitopes. We tested 194 blood samples from healthy donors and lung cancer patients with a panel of 40 BARD1 antigens. Using fitted Lasso logistic regression we determined the optimal combination of BARD1 antigens to be used in ELISA for discriminating lung cancer from healthy controls. Random selection of samples for training sets or validations sets was applied to validate the accuracy of our test. Results: Fitted Lasso logistic regression models predict high accuracy of the BARD1 autoimmune antibody test with an AUC = 0.96. Validation in independent samples provided and AUC = 0.86 and identical AUCs were obtained for combined stages 1–3 and late stage 4 lung cancers. The BARD1 antibody test is highly specific for lung cancer and not breast or ovarian cancer. Conclusion: The BARD1 lung cancer test shows higher sensitivity and specificity than previously published blood tests for lung cancer detection and/or diagnosis or CT scans, and it could detect all types and all stages of lung cancer. This BARD1 lung cancer test could therefore be further developed as i) screening test for early detection of lung cancers in high-risk groups, and ii) diagnostic aid in complementing CT scan.

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Pilyugin M, Descloux P, André PA, Laszlo V, Dome B, Hegedus B et al. BARD1 serum autoantibodies for the detection of lung cancer. PLoS One. 2017 Aug 7;12(8). e0182356. https://doi.org/10.1371/journal.pone.0182356