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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.

The high-dimensional linear model y = Xβ 0 + is considered and the focus is put on the problem of recovering the support S 0 of the sparse vector β 0 . We introduce Lasso-Zero, a new 1 -based estimator whose novelty resides in an "overfit, then threshold" paradigm and the use of noise dictionaries concatenated to X for overfitting the response. To select the threshold, we employ the quantile universal threshold based on a pivotal statistic that requires neither knowledge nor preliminary estimation of the noise level. Numerical simulations show that Lasso-Zero performs well in terms of support recovery and provides an excellent trade-off between high true positive rate and low false discovery rate compared to competitors. Our methodology is supported by theoretical results showing that when no noise dictionary is used, Lasso-Zero recovers the signs of β 0 under weaker conditions on X and S 0 than the Lasso and achieves sign consistency for correlated Gaussian designs. The use of noise dictionary improves the procedure for low signals.

We propose Robust Lasso-Zero, an extension of the Lasso-Zero methodology, initially introduced for sparse linear models, to the sparse corruptions problem. We give theoretical guarantees on the sign recovery of the parameters for a slightly simplified version of the estimator, called Thresholded Justice Pursuit. The use of Robust Lasso-Zero is showcased for variable selection with missing values in the covariates. In addition to not requiring the specification of a model for the covariates, nor estimating their covariance matrix or the noise variance, the method has the great advantage of handling missing not-at random values without specifying a parametric model. Numerical experiments and a medical application underline the relevance of Robust Lasso-Zero in such a context with few available competitors. The method is easy to use and implemented in the R library lass0.

mutations were significantly associated with adenocarcinoma histology and female never smokers (p<0.001) and KRAS mutations predominated in smokers (p<0.001). Conclusion: Driver mutations were detected in 46.8% of NSCLC cases resected at TPCH. Rapid, multiplexed mutation testing can guide treatment as well as assist in patient stratification for clinical trials.