Salivary CD5L as a Potential Non-Invasive Biomarker for Pathological Staging and Prognostic Assessment in Oral Squamous Cell Carcinoma

Background/Objectives: In Taiwan, more than 50% of patients with oral cancer seek medical help at a late stage. Reliable non-invasive biomarkers for pathological staging and disease monitoring are still lacking. This study aimed to identify a specific biomarker associated with late-stage oral cancer and to develop a non-invasive strategy for early pathological diagnosis and disease monitoring with improved patient acceptability. Methods: A total of 116 participants were enrolled, including 31 patients with early-stage oral cancer, 49 with late-stage oral cancer, and 36 healthy controls. Saliva samples were collected for proteomic analysis, and the findings were validated using ELISA and tissue immunohistochemistry. The identified biomarker was validated, and its tumor-promoting role was confirmed using malignant phenotype assays, including colony formation, soft agar, migration, and invasion assays. Results: Our results demonstrate that CD5L expression could not be distinguished between early- and late-stage groups using tissue immunohistochemistry. In contrast, salivary CD5L levels differentiated early-stage from late-stage patients noninvasively. Functional studies demonstrated that CD5L suppression markedly attenuated malignant phenotypes (colony formation, anchorage-independent growth, migration, invasion), suggesting its involvement in tumor aggressiveness and metastatic potential. Conclusions: These findings provide new insights into the pathological role of salivary CD5L in oral cancer progression and support its potential as a non-invasive biomarker for disease stratification.