ArticleJournal of translational medicine2024
Mutational variant allele frequency profile as a biomarker of response to immune checkpoint blockade in non-small cell lung Cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Guiding the Application of Immunotherapy in Nonsmall Cell Lung Cancer: The Role of Biomarkers.Thoracic cancer · 2026Review
- Identification of candidate variants in plasma associated with early versus late disease progression under anti-PD-1 therapy in metastatic NSCLC.Translational lung cancer research · 2026Article
- Baseline levels and dynamic changes of cfDNA, tumor fraction and mutations to anticipate the clinical course of small cell lung cancer (SCLC) patients treated with first-line atezolizumab and chemotherapy: an hypothesis generating study (CATS/ML43257).Journal of experimental & clinical cancer research : CR · 2025Article
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9 authors.
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Abstract
introductionIdentifying new biomarkers for predicting immune checkpoint inhibitors (ICIs) response in non-small cell lung cancer (NSCLC) is crucial. We aimed to assess the variant allele frequency (VAF)-related profile as a novel biomarker for NSCLC personalized therapy.
methodsWe utilized genomic data of 915 NSCLC patients via cBioPortal and a local cohort of 23 patients for model construction and mutational analysis. Genomic, transcriptomic data from 952 TCGA NSCLC patients, and immunofluorescence (IF) assessment with the local cohort supported mechanism analysis.
resultsUtilizing the random forest algorithm, a 15-gene VAF-related model was established, differentiating patients with durable clinical benefit (DCB) from no durable benefit (NDB). The model demonstrated robust performance, with ROC-AUC values of 0.905, 0.737, and 0.711 across training (n = 313), internal validation (n = 133), and external validation (n = 157) cohorts. Stratification by the model into high- and low-score groups correlated significantly with both progression-free survival (PFS) (training: P < 0.0001, internal validation: P < 0.0001, external validation: P = 0.0066) and overall survival (OS) (n = 341) (P < 0.0001). Notably, the stratification system was independent of PD-L1 (P < 0.0001) and TMB (P < 0.0001). High-score patients exhibited an increased DCB ratio and longer PFS across both PD-L1 and TMB subgroups. Additionally, the high-score group appeared influenced by tobacco exposure, with activated DNA damage response pathways. Whereas, immune/inflammation-related pathways were enriched in the low-score group. Tumor immune microenvironment analyses revealed higher proportions of exhausted/effector memory CD8 + T cells in the high-score group.
conclusionsThe mutational VAF profile is a promising biomarker for ICI therapy in NSCLC, with enhanced therapeutic stratification and management as a supplement to PD-L1 or TMB.
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