Late Breaking Abstract - DNA methylation in transbronchial lung biopsy tissue aids in the diagnosis of pathologically negative lung cancer: a prospective study

<bold>Background:</bold> DNA methylation shows promising value in diagnosing early lung cancer, especially using limited samples like the transbronchial biopsy. <bold>Methods:</bold> DNA methylation profiling was performed in the paired lung cancer, peritumoral tissue, and transbronchial lung biopsy samples to select the cancer-specific biomarkers. Using pathology as the gold standard, a diagnostic model was constructed with the aforementioned biomarkers to discriminate malignancy from benignity. This model was then trained in 172 tissue samples, and independently validated in 143 tissue samples. <bold>Results:</bold> We identified two lung cancer-specific methylation markers (PTGER4, ZSCAN31). Their methylation values were significantly higher in malignant tissues than in the peritumoral and normal tissues. The same trend was then observed in the transbronchial biopsy samples. A diagnostic model was then constructed based on the abovementioned biomarkers. In the test set, it achieved an area under curve (AUC) of 0.90, with a sensitivity of 72% and a specificity of 100%. In the independent validation set, the AUC was 0.85, with a specificity of 76% and a sensitivity of 88%. This model was further tested in 21 transbronchial biopsy specimens, which were false negative according to pathology. Notably, DNA methylation could correctively identify 13 malignancies, achieving an accuracy rate of 79%. <bold>Conclusions:</bold> DNA methylation can serve as a supplementary tool for traditional pathology in identifying malignant biopsy tissues.