AUTHOR=Wu Bin , Zheng Min , Guo Qingkui , Wang Ning , Zhu Chen , Zhao Wen , Xu Ye TITLE=Early potential metabolic biomarkers of T1 stage lung adenocarcinoma based on serum metabolomics JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1544774 DOI=10.3389/fmolb.2025.1544774 ISSN=2296-889X ABSTRACT=BackgroundThis study aims to investigate serum metabolite changes in patients with early-stage (T1) lung adenocarcinoma, identify potential diagnostic biomarkers, and establish an early warning mechanism for T1 stage lung adenocarcinoma.MethodsThe study included two groups: a lung adenocarcinoma group and a healthy control group. Serum samples underwent non-targeted metabolomics analysis. Total ion chromatograms (TIC) were generated to assess system stability. Chromatographic data were analyzed using multivariate statistical methods, including principal component analysis (PCA) for dimensionality reduction. Partial least squares discriminant analysis (PLS-DA) further validated PCA findings. Variables with VIP scores >1.0 in the PLS-DA model were selected, combined with ANOVA and T-tests (P < 0.05), to identify differentially expressed metabolites. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of selected metabolites.ResultsSerum metabolites significantly differed between the lung adenocarcinoma group and the healthy control group. Multivariate statistical analysis and ROC curve evaluation identified four potential diagnostic biomarkers: Cortisol, 3-Oxo-OPC4-CoA, PE-NMe(14:1(9Z)/14:1(9Z)), and Ceramide (d18:1/9Z-18:1), with AUC values of 0.930, 0.895, 0.890, and 0.795, respectively.ConclusionCortisol,3-Oxo-OPC4-CoA,PE-NMe(14:1(9Z)/14:1(9Z)), and Ceramide (d18:1/9Z-18:1) exhibit significantly altered metabolic levels in T1 stage lung adenocarcinoma patients and can serve as metabolic biomarkers. These markers may enhance the sensitivity and specificity of early diagnosis, facilitating improved detection of T1 stage lung adenocarcinoma.