Abstract Rationale Early detection of lung adenocarcinoma (LUAD) remains a critical challenge. We previously demonstrated that circulating exosomal miR-885-3p has strong diagnostic and prognostic potential in LUAD patients. However, its tissue origin and biological function remained unknown. In this study, we sought to validate these findings in a larger cohort and to determine whether exosomal miR-885-3p is tumor-derived and functionally linked to oncogenic signaling pathways. Methods Within the LUCEx project (Hospital Universitario Miguel Servet, 2020-2024), plasma and paired lung tissue samples were collected from 214 LUAD patients and 97 non-cancer subjects undergoing lung resection. Exosomes were isolated from both plasma and lung tissue (tumor and tumor-free regions) and characterized by protein markers, morphology, and nanoparticle tracking analysis. miR-885-3p levels were quantified by RT-qPCR. Bioinformatic analyses (TargetScan, KEGG, Reactome) were performed to identify functional pathways associated with miR-885-3p targets. Results Consistent with our previous findings, plasma exosomal miR-885-3p was significantly increased in LUAD patients compared with non-cancer controls (Fold Change = 6.48; p 0.001), showing excellent diagnostic accuracy (AUC = 0.844; p 0.001) with a PPV of 85% and an NPV of 56%. High miR-885-3p levels were associated with increased mortality (HR = 11.43; p 0.0001). In tissue-derived exosomes, miR-885-3p was absent in samples from healthy parenchyma but consistently detected in LUAD and carcinoid tumors, confirming its tumor origin. Functional enrichment analysis revealed regulation of PI3K/AKT, MAPK, Ras, and p53 signaling networks, supporting roles in proliferation and tumor progression. Conclusions This study validates miR-885-3p as a tumor-derived exosomal biomarker with diagnostic and prognostic relevance in LUAD. The integration of plasma and tissue findings, together with its involvement in oncogenic pathways, consolidates miR-885-3p as a robust candidate for patient stratification and monitoring in precision oncology. This abstract is funded by: None
RodrÍguez-Sanz et al. (Fri,) studied this question.