Non-invasive radiogenomic mapping of the SMARCAL1-driven ferroptotic niche is associated with longitudinal MRD-negative surveillance in early-stage NSCLC
A CT scan pattern can now predict which early-stage lung cancer patients will stay disease-free, helping guide treatment decisions.
A pre-operative CT radiomic signature was developed and externally validated as a non-invasive surrogate for an immune-active, ferroptosis-enriched tumor microenvironment associated with sustained ctDNA MRD-negative surveillance in resected early-stage NSCLC. SMARCAL1 was identified as the molecular driver, with CRISPR validation confirming its role in ferroptosis resistance and T-cell chemotaxis, offering a new non-invasive biomarker for adjuvant therapy decision-making.
What the study was
- Study design
- Translational cohort study (nested in prospective CTONG 2201 trial) with external validation
- Population
- Completely resected stage IB-IIIA NSCLC, MRD-negative at two post-operative landmarks; n=71 (derivation) + n=178 (TCIA NSCLC-Radiogenomics) + n=89 (Lung3) external validation
- Sample size
- 338
- Category
- Early Detection
- Maturity
- Validated
- Journal
- Frontiers in Immunology
Why it surfaced
Externally validated (2 independent cohorts) radiogenomic signature for non-invasive ctDNA MRD surrogate; mechanistically interrogated via spatial transcriptomics, CRISPR, and multiplex IF; outperforms existing biomarker comparators; prospective validation pending NCT05457049.
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