Metabolomic analysis of subgingival plaque, identification of diagnostic biomarkers and associated mechanisms in patients with HCC and periodontitis vs. periodontitis alone
摘要
To investigate the metabolomic characteristics of subgingival plaque in patients with both hepatocellular carcinoma (HCC) and periodontitis (PD) (hereafter referred to as HCC-PD), and to clarify the differences compared with patients with PD alone, thereby providing evidence for the association mechanism between HCC and PD and for the non-invasive auxiliary diagnosis of HCC-PD.
Method18 HCC-PD patients and 18 PD patients were recruited. Non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect subgingival plaque metabolites. Multidimensional statistical analyses (PCA, PLS-DA, OPLS-DA) were applied to compare metabolic profiles, while volcanic plots and fold-change bar charts screened differential metabolites. ROC curves evaluated diagnostic efficacy, Spearman’s correlation analyzed associations between high-discriminative metabolites and clinical parameters, and KEGG database conducted pathway enrichment.
ResultsPCA showed preliminary separation, with PLS-DA and OPLS-DA achieving complete separation. A total of 1,272 differential metabolites were identified (35 upregulated, 1,237 downregulated in HCC-PD). Upregulated Glutathione thiol strongly correlated with CAL and HCC staging (p < 0.001), while downregulated Leukotriene E4 correlated with CAL in PD alone (p < 0.001). The combined model of top 20 upregulated metabolites had an AUC of 0.9999 (95%CI: 0.9998–1.0000), and the top 20 downregulated metabolites had an AUC of 0.9966 (95%CI: 0.9944–0.9989). Differential metabolites were enriched in lipid metabolism and signal transduction pathways.
ConclusionHCC is associated with distinct metabolic profiles of subgingival plaque, which may be linked to systemic metabolic dysregulation. The identified differential metabolites represent potential preliminary non-invasive diagnostic candidates for HCC-PD, while lipid metabolism pathways may constitute the core mechanism linking both conditions. However, the diagnostic efficacy of these candidates needs to be further verified in large-scale multi-center studies.