ArticleRespiratory research2025
Exploring a mutation-based signature to predict the benefits of immune checkpoint inhibitors in oncogene-addicted subsets of non-small cell lung cancer: a retrospective study.
Article in Respiratory research, 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
backgroundDespite the effectiveness of immune checkpoint blockade (ICB) therapy in cancer treatment, oncogene-addicted subsets of non-small cell lung cancer (NSCLC) typically derive limited benefits. Herein, we established and evaluated a mutation-based signature to predict ICB efficacy in patients with both non-mutant and oncogene-mutant NSCLC.
methodsThe predictive power of the signature was evaluated and validated across advanced NSCLCs cases with or without targetable oncogene alterations, using four public and one in-house immunotherapy cohort. NSCLC cohorts from The Cancer Genome Atlas were used to explore the underlying mechanisms of the signature. Herein, we defined a gene mutation number (GMN) based on the signature and classified patients into high and low GNM groups (GMN-H and GMN-L, respectively).
resultsThe GMN-H group exhibited significantly improved overall survival (OS) (hazard ratio [HR], 0.23; 95% confidence interval [CI]: 0.14-0.37; P < 0.001 in the discovery cohort) and progression-free survival (HR, 0.43; 95% CI: 0.28-0.65; P < 0.001 in the discovery cohort; HR, 0.41; 95% CI: 0.26-0.66; P = 0.0011 in the validation cohort) after ICB therapy. The survival advantage of GMN-H persisted in patients with KRAS mutations, whereas only trends toward improved survival outcomes were observed in those with EGFR, HER2, or MET alterations. Moreover, in the KRAS
conclusionsThe mutation-based signature established herein represents a robust biomarker for identifying patients with advanced NSCLCs who are most likely to benefit from ICB therapy, including those with targetable oncogene alterations.
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