From discovery to clinical implementation: a bibliometric analysis of DNA methylation biomarkers in non-small cell lung cancer, 1999-2025.

BACKGROUND

DNA methylation alterations are stable, biologically informative, and detectable in tissue and circulating DNA, making them promising biomarkers for non-small cell lung cancer (NSCLC). However, few methylation biomarkers have entered routine clinical practice. We aimed to characterize the evolution and translational challenges of this field.

METHODS

Publications on NSCLC, DNA methylation, and biomarker applications were retrieved from the Web of Science Core Collection through 31 December 2025. After PRISMA-based screening, bibliometric and knowledge-map analyses were performed.

RESULTS

A total of 1,910 publications were included. Annual output increased after 2010 and peaked in 2022. Lung Cancer was the most productive journal, whereas Cancer Research had the highest citation impact. China contributed the largest publication volume, while the United States had the highest citation impact. Foundational studies focused on promoter hypermethylation, methylation-specific PCR, and methylated DNA detection in accessible biospecimens. Research priorities shifted from candidate-gene studies toward methylation signatures, liquid biopsy, multi-omics integration, immunotherapy-related applications, and computational modeling.

CONCLUSION

NSCLC methylation biomarker research has evolved toward integrated translational frameworks. Future progress requires multicenter validation, standardized platforms, clinically defined methylation panels, and AI-assisted integration.

PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD420261426546.