This project, RNA Pathology, aims to establish a new spatially resolved framework for diagnosing and understanding lung adenocarcinoma (LUAD) progression. LUAD evolves through a histopathological continuum from pre-invasive (AAH/AIS) to minimally invasive (MIA) and fully invasive stages. However, defining invasion remains highly subjective by morphology alone. To overcome this limitation, the project integrates histopathology with high-resolution spatial transcriptomics to generate RNA-based maps of invasion programs and tumour–stroma interactions directly in FFPE sections.
Building on the Nilsson Group’s pioneering in situ sequencing (ISS) and Xenium platforms, we will construct a spatial atlas of the LUAD continuum and identify robust invasion-associated signatures. A dedicated bioinformatic pipeline, EXACT (Expandable Cross-sample Analysis for Clinical Spatiomics Data), will align pathology-annotated samples across patients to extract reproducible molecular features linked to clinical covariates. These data will yield a minimal diagnostic marker panel for routine pathology, enabling more objective and reproducible assessment of invasion.
The project combines thoracic pathology, spatial omics, and computational biology to translate discovery-scale molecular data into clinical tools. Expected outcomes include two manuscripts, open-source pipelines, and a pathology-ready diagnostic panel. Ultimately, RNA Pathology will contribute to precision oncology and establish RNA-based diagnostics as a robust complement to conventional histopathology.