BARD1 serum autoantibodies for the detection of lung cancer

Abstract

PurposeCurrently 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.MethodsELISA 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.ResultsFitted 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.ConclusionThe 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.

Dualistic Role of BARD1 in Cancer

“…The over-expression of BARD1 isoforms is strongly correlated with tumor progression, specifically in non-small-cell lung cancer (NSCLC) [ 20 , 51 , 78 ]. Based on these evidences Irminger-Finger et al have developed a blood test for the early detection and diagnosis of lung cancer based on capturing autoimmune antibodies against BARD1 antigens [ 91 ]. Additional studies are needed to verify the efficacy of this test in detection of lung cancer and it will be very interesting to extend this experimentation to other cancers such as neuroblastoma, ovarian and breast cancer.…”

Elderly with COPD: comoborbitidies and systemic consequences

“…Certainly, lung cancer is five times more common in smokers with COPD than in those with normal lung function 61,62 and COPD is an independent risk factor for lung carcinoma, mostly for squamous cell carcinoma 63 . Despite the advances in early identification and in the therapeutic management of both COPD and lung cancer the underlying networking mechanisms are far from being well established resulting in poor prognosis [64][65][66][67][68][69] . Many epidemiological studies have showed that emphysema and air flow obstruction are both involved as risk factors for lung cancer incidence and death, but their relative roles have not been fully clarified.…”

BARD1 and Breast Cancer: The Possibility of Creating Screening Tests and New Preventive and Therapeutic Pathways for Predisposed Women

“…The above phenomenon may correlate with the fact that BARD1 functions as a factor of apoptosis, unrelated to BRCA1. Isoforms excessively expressed in tumor cells do not have suppressor functions, which leads to faster progression and poor prognosis [43,44,4]. [48].…”