Discovery of potential serum protein biomarkers for lymph node metastasis in oral cancer

ABSTRACT Background 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. Methods 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. Results 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. Conclusion 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. © 2015 Wiley Periodicals, Inc. Head Neck 38: 118–125, 2016