ArticleJournal of experimental & clinical cancer research : CR2025
Low-coverage whole genome sequencing of cell-free DNA to predict and track immunotherapy response in advanced non-small cell lung cancer.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Genome-wide variation in cell-free DNA end-motif entropy predicts immunotherapy response in head and neck cancer.The Journal of clinical investigation · 2026Trial
- Applications of circulating tumor DNA in unresectable and advanced non-small cell lung cancer immunotherapy: from stratification to therapeutic guidance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cell-free DNA genomic and fragmentomic features for early outcome prediction in large B cell lymphoma.Cell reports. Medicine · 2026Article
- Genome-Wide Variations of End Motif in Cell-Free DNA Fragments Distinguish Immunotherapy Responders from Non-Responders in Head and Neck Cancer: A Multi-Institute Prospective Study.medRxiv : the preprint server for health sciences · 2026Article
- Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer.NPJ precision oncology · 2026Article
- The progress of biomarkers detection to lung cancer.Discover oncology · 2026Review
- [Appropriate Duration of First-line Immunotherapy for Advanced NSCLC and Predictive Factors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Bibliometric analysis of research trends and hotspots in immunotherapy biomarkers for non-small cell lung cancer from 2015 to 2024.Discover oncology · 2026Article
- Integrative multiomic profiling of cfDNA methylation and EV-miRNAs identifies immunotherapy-outcome molecular subtypes in NSCLC.Journal for immunotherapy of cancer · 2026Article
- Evolving non-invasive biomarkers in NSCLC immunotherapy: integrating liquid biopsy and multi-omics profiling for precision oncology.Frontiers in immunology · 2026Review
- Cell-Free DNA (cfDNA), Its Applications in Cancer Diagnosis and Monitoring, and Its Potential Role in Regulating Cancer Metabolism.Advances in experimental medicine and biology · 2026Review
- Genomics and Epigenomics Approaches for the Quantification of Circulating Tumor DNA in Liquid Biopsy: Relevance of a Multimodal Strategy.International journal of molecular sciences · 2025Review
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOutcomes under anti-PD-(L)1 therapy have been variable in advanced non-small cell lung cancer (NSCLC) without reliable predictive biomarkers so far. Targeted next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has demonstrated potential clinical utility to support clinical decisions, but requires prior tumor genetic profiling for proper interpretation, and wide adoption remains limited due to high costs.
methodsTumor-agnostic low-coverage ctDNA whole genome sequencing (lcWGS) was used to longitudinally track genome-wide copy number variations (CNVs) and fragmentation features in advanced NSCLC patients (n = 118 samples from 49 patients) and healthy controls (n = 57). Tumor PD-L1 expression was available for comparison.
findingsFragmentation features and CNVs were complementary indicators, whose combination significantly increased ctDNA detection compared to single-marker assessments (+ 20.3% compared to CNV analysis alone). Baseline fragment length alterations, but not CNVs, were significantly associated with subsequent progression-free survival (PFS; hazard ratio [HR] = 4.10, p = 6.58e-05) and could improve PFS predictions based on tumor PD-L1 expression alone (HR = 2.70, p = 0.019). Residual CNVs or aberrant fragmentation of ctDNA under ongoing therapy could stratify patients according to the subsequent response duration (median 5.8 vs. 47.0 months, p = 1.13e-06). The integrative analysis of ctDNA fragment characteristics at baseline, tumor PD-L1 expression, and residual ctDNA under ongoing treatment constituted the strongest independent predictor of PFS (p = 6.25e-05) and overall survival (p = 1.3e-03) in multivariable analyses along with other clinicopathologic variables.
interpretationThis study demonstrates the feasibility and potential clinical utility of lcWGS for the tumor-agnostic stratification and monitoring of advanced NSCLC under PD-(L)1 blockade based on CNV and fragmentomic profiling.
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