Data Sheet 1_Multi-cohort machine learning identifies a ferroptosis-linked prognostic signature in lung adenocarcinoma.pdf

The highest cohort-specific C-indices among the prespecified candidate configurations were 0.611, 0.691, and 0.699 and arose from different model configurations. Applying the same development-selected configuration to all three external cohorts yielded Harrell’s C-indices of 0.605, 0.675, and 0.682 and 5-year Uno’s C-indices of 0.605, 0.678, and 0.696. In TCGA-LUAD, the stored out-of-fold molecular score remained prognostic after TNM stage adjustment (hazard ratio per standard deviation 2.32, 95% confidence interval: 1.39−3.87; p = 0.0013).</p>Discussion<p>At 3 years and 5 years, the combined TNM-plus-score models showed close calibration and modest gains in discrimination, while decision-curve analysis identified positive incremental net benefit only over restricted threshold ranges.

Low-risk tumors were enriched for interferon, complement, and immune-cell programs. These computational findings require further prospective assay-level and experimental validation before clinical implementation.</p>