Epigenetic Imprinted Gene Biomarkers Significantly Improve The Accuracy Of Presurgical Bronchoscopy Diagnosis Of Lung Cancer.

e21055 Background: The ability to diagnose earlier stages of carcinogenesis using less invasive presurgical tissue samples is especially desirable, but is often inconclusive because of insufficient morphological evidences of cancer. Many of the epigenetic biomarkers are involved in lung cancer, but are challenging to clinically evaluate. In this study, Quantitative Chromogenic Imprinting Gene In-Situ Hybridization (QCIGISH) was applied to directly visualize and quantitatively assess the biallelic and multiallelic alterations of imprinted gene expressions in order to characterize lung cancer carcinogenesis and progression. We updated an imprinted gene panel and developed an accurate lung cancer diagnostic grading model from minimally invasive biopsies using the QCIGISH method. Methods: 225 surgical (151 lung cancer, 74 benign lung lesion) and 95 pre-surgical samples (77 lung cancer, 18 benign lung lesion) were collected from 320 patients under clinical trial NCT03882684 involving five medical centers between 2015 and 2019. The QCIGISH method was applied to detect the allelic expression status of the GNAS, GRB10, SNRPN and HM13 imprinted gene panel. A diagnostic grading model for lung cancer progression was trained using 225 retrospectively collected surgical tissue set with known diagnosis, refined using 25 presurgical samples, and blindly validated using 70 presurgical samples. Results: The diagnostic grading model collectively achieved high sensitivity (98.7%) which is significantly higher than standard presurgical bronchoscopy diagnostic methods including transbronchial brushing (58-74%), transbronchial biopsy (61-75%), alveolar lavage (35-64%) and the combination of the aforementioned three methods (64-80%). Thus, epigenetic imprinted gene biomarkers significantly improve bronchoscopy diagnostic accuracy by 18.7% (98.7% vs 80%), while demonstrating even higher specificity (100% vs 94-96%). Conclusions: Epigenetic imprinted gene biomarkers are shown to be highly accurate in effectively differentiating benign lesions and malignant lung cancer cases. In addition, the improved accuracy demonstrated by QCIGISH over standard presurgical bronchoscopy diagnostic procedures makes it a viable and revolutionary epigenetics-based cancer detection method for practical clinical applications especially for small samples and less advanced grades of lung cancer.