Gingival Crevicular Fluid Proteomic Shift: From Gingivitis to Periodontitis

INTRODUCTION AND AIMS: Gingivitis is a reversible, mild inflammation, whereas periodontitis is a chronic condition with irreversible tissue destruction. Despite the widespread use of clinical indicators, their lack of molecular specificity limits mechanistic diagnosis. Gingival crevicular fluid, a noninvasive medium reflecting localized immune activity, has been insufficiently explored in proteomic studies to distinguish gingivitis from periodontitis. This study revealed quantitative proteomics and network analysis to identify distinct molecular characteristics differentiating the two conditions. METHODS: We analysed 72 gingival crevicular fluid samples from healthy, gingivitis, and periodontitis groups using liquid chromatography-mass spectrometry and integrated bioinformatic analysis, including differential expression analysis, weighted gene coexpression network analysis, and protein-protein interaction network analysis. RESULTS: Among 649 identified proteins, differential expression analysis revealed significant upregulation of proteins such as RAC2 and S100A12 in periodontitis. Weighted gene coexpression network analysis identified distinct molecular modules associated with each disease stage. Gingivitis showed enrichment of complement-related proteins, while periodontitis was characterized by neutrophil-associated protein modules, demonstrating a complement-to-neutrophil shift with disease progression. Protein-protein interaction network analysis confirmed the central roles of hub proteins such as LCN2 and RAC2, and receiver operating characteristic curve analysis supported their potential as discriminatory markers. CONCLUSIONS: These results demonstrate stage-specific proteomic shifts in periodontal disease progression, offering molecular insights for objective diagnosis and therapeutic targeting. The observed complement-to-neutrophil transition enables differentiation between disease stages, which current clinical markers fail to achieve. These proteomic markers provide molecular evidence of progression, potentially enhancing early intervention and guiding treatment beyond conventional clinical assessments. CLINICAL RELEVANCE: This proteomic profiling reveals complement-to-neutrophil transition from gingivitis to periodontitis, enabling stage-specific diagnosis since current clinical markers cannot distinguish inflammatory mechanisms. The identified protein markers are likely to provide objective molecular evidence for evaluating disease progression, potentially improving early intervention timing and treatment selection compared to traditional clinical measurements alone.