ArticleJCO precision oncology2025
Hypoxic Gene Expression Signature as a Predictor of Recurrence and Mortality in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.
Article in JCO precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeRecurrence occurs in 20%-30% of early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Hypoxia in the tumor microenvironment drives radiation resistance, immune evasion, and tumor progression. Biomarkers measuring hypoxia may be useful for prognostication of NSCLC treated with SBRT. We investigate an RNA-based approach to measure tumor hypoxia and associate these molecular biomarkers with clinical outcomes after SBRT.
methodsWe included patients with T1-3N0 NSCLC treated with SBRT. RNA isolated from formalin-fixed paraffin-embedded tumor biopsy specimens (pretreatment) was analyzed using the Clariom-D assay. Hypoxia scores were derived using three well-established gene signatures measuring hypoxia and risk scores were median-dichotomized. Kaplan-Meier and Cox proportional hazards were used to study the association between high hypoxia scores and tumor recurrence and survival.
resultsWe included 92 patients treated between 2008 and 2018 with a median follow-up of 23.9 months. All three signatures were associated with squamous histology (
conclusionWe demonstrate squamous histology is associated with RNA-based hypoxic gene signatures, and that the Lane RNA-based hypoxia signature is highly prognostic of disease progression and mortality in NSCLC treated with SBRT, which merits prospective validation.
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