Characterization of Biomarkers Indicative of Tumor Progression, Epithelial to Mesenchymal Transition, and Response to Cytotoxic Drugs in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancers that predominantly affects men and accounts for over 50,000 new cancer cases annually in the United States. Survival rates are markedly different for localized OSCC versus metastatic disease, for which five-year survival is only 39%. Depending on pathology and stage at diagnosis, treatment may involve surgery, radiation, targeted therapy, or conventional chemotherapy. However, there is an unmet need for reliable biomarkers to predict treatment response or link therapeutic efficacy to tumor progression. We sought to identify novel OSCC tumor progression biomarkers that correlate with epithelial to mesenchymal transition (EMT) and response to cytotoxic drugs. Using four cell lines that represent the stepwise progression from normal oral mucosa to dysplastic, invasive, and metastatic OSCC lesions, we found that expression of Stratifin, a tumor suppressor gene, is inversely correlated with both tumor progression steps and the expression of the EMT marker N-cadherin. Conversely, E-cadherin and fibronectin expression were markedly decreased in advanced stage OSCC lines. In addition, metastatic Detroit 562 cells exhibited resistance to docetaxel and showed clear migratory behavior. In summary, here we describe a unique molecular signature of advanced and drug-resistant OSCC tumors, which might help predict clinical outcomes and guide treatment options for patients afflicted with oral cancer.