The purpose of our study was to identify serum protein biomarkers for node-positive oral squamous cell carcinoma (OSCC). Biomarkers indicating lymph node metastasis provides a valuable classification methodology to optimize treatment plans for patients with OSCC.

Quantitative serum proteomic analysis of OSCCs with either node-positive or node-negative disease was performed with tandem mass spectrometry and isobaric tagging for relative and absolute quantitation (iTRAQ). Immunoassays were used to validate a panel of candidate protein biomarkers and receiver operating characteristic (ROC) analysis was used to evaluate the performance of the candidate biomarkers.

A total of 282 serum proteins were quantified between node-positive and node-negative OSCCs with the proteomic approach. Four candidate biomarkers, gelsolin, fibronectin, angiotensinogen, and haptoglobin, were validated in an independent group of patients with node-positive or node-negative OSCC. The best candidate biomarker, gelsolin, yielded a ROC value of 89% for node-positive OSCC, although the sample size for validation is relatively small. Fibronectin, gelsolin, and angiotensinogen were also found to be differentially expressed between cancer cell lines of node-positive and node-negative cancer origin.

Our studies suggest that testing of serum protein biomarkers might help detect lymph node metastasis of oral cancer. Because of limited sample size in our studies, long-term longitudinal studies with large populations of individuals with oral cancer are needed to validate these potential biomarkers.