AUTHOR=Ye Lingyun , Hu Xinnan , Chen Shen , Wang Hai , Li Juanjuan , Wang Lei , Gao Guanghui , Chen Xiaoxia , Song Xiao TITLE=Exploration of patient plasma exosomes as biomarkers for predicting lung cancer brain metastasis JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1687866 DOI=10.3389/fmed.2025.1687866 ISSN=2296-858X ABSTRACT=BackgroundMany studies have found that exosomes have numerous advantages in the early diagnosis of tumors. We detected and analyzed plasma exosomes from lung cancer patients to identify potential biomarkers that could predict brain metastasis.MethodThe total RNA of plasma exosomes of advanced lung cancer patients was extracted and sequenced. The BLAST software was used to align the predicted target gene sequence against the GO and KEGG databases, thereby acquiring annotation details for the target genes. The selected exosomal miRNAs and short-chain fatty acids were subjected to diagnostic performance validation analysis.ResultsExosomal miR-223-3p, miR-27a-3p, and miR-27b-3p were significantly increased in the plasma exosomes of lung cancer patients with brain metastasis. The concentrations of isobutyric acid (IBA), valeric acid (VA), isovaleric acid (IVA), and acetic acid (AA) were markedly elevated in the plasma exosomes of lung cancer patients with brain metastasis. Spearman correlation analysis revealed that both miR-27a-3p and miR-27b-3p had significant associations with IVA and VA. A multi-biomarker model combining the selected exosomal miRNAs with metabolic molecules could improve the diagnostic performance with an AUC of 0.927.ConclusionPlasma exosomal miR-223-3p, miR-27a-3p, miR-27b-3p, and IBA, IVA, VA, and AA in advanced patients are closely associated with brain metastasis and have the potential to act as biomarkers for predicting brain metastasis in lung cancer patients.