Concordance of genomic mutations between tissue and ctDNA in non-small cell lung cancer: impact of time interval stratified by stage, smoking history and treatment

Abstract

Abstract Purpose The concordance between tumor tissue and liquid biopsies has been extensively investigated in previous studies. Among the influential factors, the time interval between tissue and blood draw has received significant attention, but its impact on the concordance between tissue and liquid biopsies has yielded inconsistent results. In this study, we aimed to evaluate the effect of the time interval between tissue and blood draw on the concordance between tissue and liquid biopsies while adjusting potential confounding factors such as clinical stage, smoking history, and treatment. Methods A total of 116 paired tissue and plasma lung cancer samples were collected from Beijing Chest Hospital and sequenced by hybridization capture-based next-generation sequencing (NGS) using a targeted enrichment panel covering 20 lung cancer-related genes. Mutation profiles obtained from tissue and circulating tumor DNA (ctDNA) were compared. The impact of time interval between tissue and blood draw on the concordance between tissue and liquid biopsies was assessed, stratifying the analysis based on clinical stage, smoking history, and treatment using the Cochran-Mantel-Haenszel test. Results ctDNA was detected in 49.14% (57/116) of clinical lung cancer samples. TP53 and EGFR carried the most mutations, both in tissue and ctDNA. Among the tissue mutations, 37.39% (83/222) were detected in paired ctDNA samples, while 89.25% (83/93) of ctDNA mutations were detected in paired tissue samples. The stratified analysis results demonstrated a significant correlation between concordance rates and the time interval between tissue and blood draw when stratified by clinical stage (P < 0.001, Cochran-Mantel-Haenszel test). Additionally, the genomic characteristics observed in tissue and ctDNA samples from two clinical lung cancer patients exhibited tumor heterogeneity. Conclusion The time interval between tissue and blood draw had a significant impact on the concordance between tissue and liquid biopsies when stratified by clinical stage. Furthermore, ctDNA demonstrated the ability to overcome tumor heterogeneity to some extent, indicating its potential as a viable alternative to tissue biopsies when tumor tissue is not accessible.