Putative Biomarkers for Prognosis, Epithelial-to-Mesenchymal Transition, and Drug Response in Cell Lines Representing...

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer and accounts for over 50,000 new cancer cases annually in the United States. The survival rates are markedly different for localized OSCC versus metastatic disease, for which the five-year survival rate is only 39%. Depending on its pathology and stage at diagnosis, the treatment may involve surgery, radiation, targeted therapy, or conventional chemotherapy. However, there is an unmet need for reliable biomarkers to predict the treatment response or link therapeutic efficacy to tumor progression. We sought to assemble a panel of OSCC tumor progression biomarkers that correlated with the epithelial-to-mesenchymal transition (EMT) and the response to cytotoxic drugs.

We used four cell lines that represented the stepwise progression from normal oral mucosa to dysplastic, invasive, and metastatic OSCC lesions and performed a quantitative analysis via Western blot for putative markers. EMT phenotypes were assessed using wound healing migration assays. Live cell imaging was used to assess drug effectiveness over time.

The 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, the E-cadherin and fibronectin expression was markedly decreased in the advanced-stage OSCC lines. In addition, metastatic Detroit 562 cells exhibited resistance to cell death following docetaxel treatment and showed clear migratory behavior.

We describe a molecular signature of advanced and drug-resistant OSCC tumors which encompasses multiple markers, warranting further investigation to establish their utility in predicting clinical outcomes and guiding the treatment options for patients afflicted with oral cancer.