Discovery of Serum Exosomal Protein Biomarkers for Early- and Late-Stage Lung Cancer Through Comparative Proteomic Analysis.

BACKGROUND

Lung adenocarcinoma (LUAD) exhibits distinct immune microenvironments in early-stage (ES-LUAD), advanced-stage (AS-LUAD), and pneumonia (PNA). Tumor-derived exosomes facilitate intercellular communication and contribute to the development and progression of tumors.

OBJECTIVES

This study aims to comprehensively profile and compare the serum exosomal proteome across ESLUAD, AS-LUAD, and PNA patients, identify differentially expressed exosomal proteins (DEEPs) with potential as stage-specific diagnostic and prognostic biomarkers, and elucidate the biological pathways associated with LUAD progression through functional enrichment analysis of the identified DEEPs.

METHODS

Exosomes were extracted from blood samples and characterized using TEM, NTA, and Western blotting. Proteomic analysis was performed via LC-MS-MS, and differentially expressed genes (DEGs) were analyzed using hierarchical clustering, Gene Ontology (GO), and KEGG pathway analysis.

RESULTS

Distinct exosomal protein signatures were identified across LUAD stages and PNA. CD81 and IGLV7- 46 were identified as potential biomarkers for early detection, staging, and prognosis. GO analysis revealed significant dysregulation in immune response, leukocyte activation, and response to stimuli, with cellular components implicating the extracellular matrix and cell-cell interactions. KEGG analysis highlighted differences in adrenergic signaling.

DISCUSSION: This study aims to comprehensively profile and compare the serum exosomal proteome across ESLUAD, AS-LUAD, and PNA patients; identify differentially expressed exosomal proteins (DEEPs) with potential as stage-specific diagnostic and prognostic biomarkers; and elucidate the biological pathways associated with LUAD progression through functional enrichment analysis of identified DEEPs.

CONCLUSION

Stage-specific serum exosomal protein alterations reflect LUAD biology and show strong potential as non-invasive diagnostic and prognostic biomarkers, advancing understanding and offering tools for early detection and monitoring. Clinical validation is still required.