Analysis of clinicopathological characteristics in postoperative molecular residual disease-positive stage I non-small cell lung cancer patients

Background: Multiple primary lung cancers (MPLCs) present unique clinical difficulties because of their genetically diverse independent tumors, requiring genetic testing to distinguish synchronous primaries from intrapulmonary metastases. While circulating tumor DNA (ctDNA) analysis shows potential for detecting molecular residual disease (MRD), tumor heterogeneity hinders its application. Thus, there is an urgent need to develop specific biomarkers and standardize liquid biopsy protocols to improve monitoring and treatment. The aim of this study was to analyze the clinicopathological characteristics of postoperative MRD-positive stage I non-small cell lung cancer (NSCLC) patients, with a focus on the potential utility of ctDNA in detecting MRD and guiding therapeutic decisions. Methods: Twelve patients with pulmonary nodules were analyzed. Paired tissue and plasma samples underwent genomic profiling via next-generation sequencing (NGS) using validated extraction/library preparation kits, following ethical standards. Rigorous quality controls were implemented to ensure sensitive variant detection. Results: mutations. Multiple nodules had significantly higher tumor mutational burden and clonal heterogeneity. Patients with positive MRD showed markedly elevated ctDNA levels, with clonal dynamics indicating increased shedding in multifocal disease. Conclusions: Multifocal lung disease exhibits greater genomic complexity and enhanced ctDNA shedding, supporting its use as a disease-tracking tool. The findings identify actionable signatures for MRD surveillance and guide personalized therapeutic interventions based on observed clonal architectures.