Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma.

ABSTRACT

BACKGROUND: Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated. METHODS: COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis. RESULTS: No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival. CONCLUSION: Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.