S100p Promotes The Malignant Transformation Of Oral Leukoplakia

To identify molecular biomarkers for predicting oral leukoplakia (OLK) malignant transformation risk and investigate their tumor-promoting mechanisms. Tissue and saliva samples were collected from OLK, OLK with dysplasia (OLK-D), and oral squamous cell carcinoma (OSCC) patients. A 4D-DIA-based proteomic profiling of 18 clinical tissue specimens (5 OLK, 7 OLK-D, and 6 OSCC) was conducted to delineate the proteomic landscape during OLK malignant progression, leading to the identification of S100P as a pivotal differential protein. IHC analysis validated S100P expression in 108 tissue specimens, while ELISA detected S100P levels in 96 saliva samples. Functional assays (CCK-8, colony formation, transwell) of S100P/RAGE axis used HNSCC (HN6, CAL27) and OLK-derived DOK cells. THP-1-derived macrophages were co-cultured with epithelial cells for epithelial-macrophage interaction studies. Statistical analyses used t-tests, ANOVA, and chi-square tests (SPSS v27; p<0.05 significant). This study was approved by the Ethics Committee of Nanjing Medical University. S100P showed progressive upregulation during OLK transformation correlating with advanced tumor stage (p=0.036) and size (p=0.039). S100P-RAGE activation enhanced proliferation, migration, and invasion in OLK/OSCC cells, reversible by RAGE inhibitor FPS-ZM1. Epithelial cells induced S100P secretion in M2 macrophages, revealing a stromal-epithelial crosstalk mechanism. S100P serves as a promising biomarker for OLK malignant transformation. OLK/OSCC epithelial cells stimulate S100P expression in M2 macrophages, promoting carcinogenesis via RAGE-mediated paracrine signaling.