Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer - PubMed
3 hours ago
- #tumor microenvironment
- #lineage plasticity
- #spatial multi-omics
- Combined small-cell lung cancer (cSCLC) is an aggressive subtype with mixed histologic components, managed similarly to SCLC despite poorer prognosis and limited molecular insights.
- Study uses spatial whole-exome sequencing, spatial transcriptomics, and single-nucleus RNA sequencing on 19 treatment-naïve cSCLC tumors.
- Different histologic components share a monoclonal origin, but divergence is associated with distinct mutation and copy-number alteration patterns.
- Spatially exclusive or interspersed tumor domains identified with distinct tumor microenvironment (TME) and immune landscapes.
- Fibroblast-rich boundaries enriched for an aggressive fibroblast subtype may shape TME and treatment responses.
- Lineage plasticity observed, including adenocarcinoma-to-SCLC transdifferentiation and SCLC-subtype coexistence.
- cSCLC Detector, a sensitive mutation-based assay developed to improve cSCLC detection in tissue and liquid biopsies.
- Findings illuminate cSCLC evolution and heterogeneity, underscoring the need for tailored diagnostic and therapeutic strategies.