A multivariate cell-based assay for blood-based diagnostics enhances lung cancer risk stratification

We developed the LC-iCAP, novel approach for liquid biopsies that uses cultured cells as biosensors. The cells detect cancer signals in serum and transduce them into standardized gene expression profiles, which are analyzed by machine learning for disease classification. The assay is inexpensive and scalable and has a multivariate readout with potential utility for precision medicine and multi-cancer early detection.A LC-iCAP-based lung cancer risk classifier demonstrated improved specificity compared to existing tests, suggesting meaningful clinical utility for managing indeterminate pulmonary nodules.We identified a lung-cancer specific transcriptional response to hypoxia in the assay readout, implicating HIF1A and HIF2A activity in the response consistent with known lung cancer biology and highlighting the platform's mechanistic relevance.Standardized controls and validation studies demonstrated assay reproducibility, lineage stability, and detection of technical errors-supporting the platform's readiness for clinical deployment.