Exploration of the immunogenomics connection between chronic obstructive pulmonary disease and lung cancer: The role of liquid biopsy in early diagnosis and precision prognosis

Background Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are among the most prevalent and lethal respiratory disorders worldwide. COPD patients present a significantly higher risk of developing LC, and coexistence of both diseases results in poor clinical outcomes and limited therapeutic options. Early detection remains challenging, and current diagnostic tools are often invasive or lack sensitivity. This review aims to systematically explore the immunogenomic mechanisms linking COPD and LC and to evaluate the transformative potential of liquid biopsy, framed within the holistic “circulome” concept, for early diagnosis and precision prognosis. Methods A comprehensive narrative review of peer-reviewed literature was conducted. We synthesized findings on the major components of liquid biopsy—including circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), extracellular vesicles (EVs), circulating tumor cells (CTCs), proteins, and metabolites. We specifically examined their roles in detecting genetic, epigenetic, transcriptomic, proteomic, and metabolic signatures that reflect tumor biology and host immune dysregulation in the context of COPD-associated LC. Results This review reveals a complex immunogenomic crosstalk between COPD and LC, characterized by chronic inflammation, immune evasion, and shared genetic susceptibilities. Liquid biopsy components demonstrate significant promise in capturing this dynamic interplay. Circulating nucleic acids (ctDNA/cfDNA) enable the detection of actionable mutations and epigenetic changes, while EVs and CTCs provide insights into the tumor's metastatic potential and heterogeneity. Proteomic and metabolic signatures offer complementary information on the systemic host response. The integrated “circulome” approach provides a more comprehensive framework than single-biomarker strategies, showing potential for non-invasive early detection, real-time monitoring of treatment response and improved prognostic stratification in high-risk COPD patients. Conclusion The immunogenomic connection between COPD and LC is a fertile ground for biomarker discovery. Liquid biopsy, particularly when analyzed through an integrated circulome lens, holds immense potential to revolutionize early diagnosis and enable precision medicine for this high-risk patient population. However, clinical translation is hindered by challenges in assay standardization, analytical validity, and the need for large-scale prospective validation. Future research should focus on developing multi-analyte panels and integrating artificial intelligence to refine risk prediction models and ultimately improve patient outcomes.