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These analyses do not support a robust independent prognostic claim for PDCD4 or the clinical use of any of the five evaluated genes and external prognostic replication was not established.
HELLS shows a subtype-dependent prognostic and molecular association in NSCLC, with the strongest and most reproducible signal in LUAD; however, its prognostic value is attenuated after multivariable adjustment and is not consistently reproduced across external cohorts.
Its favorable association with survival in LUAD was robust across dichotomized and continuous analyses, multivariable adjustment, EGFR-mutation sensitivity analysis, and independent GEO cohorts, and these findings support further evaluation of ADGRD1 as a subtype-specific prognostic marker, particularly in LUAD.
Higher CDKL2 expression showed a favorable prognostic association in LUAD, with consistent TCGA sensitivity analyses and limited but suggestive independent-cohort support, and CDKL2 should be regarded as a candidate prognostically associated marker rather than an established clinical biomarker.
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