A80-2-16 Biospecimen Collection and Multi-omic Analysis in an Irish Lung Cancer Screening Population

Abstract Rationale Lung cancer remains the leading cause of cancer mortality worldwide. Low-dose CT screening aims to increase early-stage detection and improve curative outcomes but presents challenges, including managing indeterminate pulmonary nodules requiring repeated imaging and invasive testing. Molecular biomarkers offer potential to enhance screening accuracy by reducing false positives and improving sensitivity, though remain investigational. Methods/Cohort Description Biospecimens are collected through recruitment at a mobile lung cancer screening unit. Blood, sputum and exhaled breath condensate (EBC) are obtained within three hours before processing. Blood is processed into serum, plasma, buffy coat, and whole blood. Patients referred from screening to rapid lung cancer clinics or undergoing diagnostic bronchoscopy are also captured for additional specimens, including oral rinse, background bronchoscope control, and bronchoalveolar lavage fluid (BALF). Demographic, clinical, and treatment data are systematically recorded. Standardized sample collection and procedural controls (e.g., bronchoscope background rinses) minimize contamination following American Thoracic Society guidelines. Samples are stored at –80 °C. Planned Analysis Microbial and host biomarkers will be analyzed to predict diagnosis of lung cancer, with further prospective analysis regarding recurrence and treatment response. Bio-specimens will undergo metagenomic, metatranscriptomic, metabolomic, and transcriptomic profiling using whole genome sequencing, RNA sequencing and Liquid chromatography–mass spectrometry (LC-MS). Predictive modeling will evaluate the utility of microbiome signatures for lung cancer detection. Integration of biospecimen and clinical data will enable biomarker validation and exploration of non-invasive diagnostic approaches Results To date, 370 patients have provided paired blood and EBC samples, and 577 sputum samples have been collected. Seven patients have undergone bronchoscopy sampling. Of this cohort, 5 new lung cancers have been diagnosed (3 adenocarcinoma, 2 squamous cell carcinoma), with 3 stage I cases referred for surgery. Six additional patients await histological confirmation, and 80 patients with indeterminate nodules remain under surveillance. Conclusions This study establishes a reproducible, evidence-based protocol for collecting invasive and non-invasive biospecimens to support multi-omic analysis. The integrated dataset aims to advance development of novel, non-invasive biomarkers for lung cancer detection and prognosis. This abstract is funded by: Irish Cancer Society & EU4Health SOLACE consortium funded screening pilot.