Loss of nuclear expression of Krüppel-like factor 4 is associated with poor prognosis in patients with oral cancer

Krüppel-like factor 4 is not only involved in cell proliferation but also affects cell differentiation and extracellular matrix production via positive and negative regulation of the expression of a wide range of genes. To our knowledge, little information is available regarding the role of Krüppel-like factor 4 in oral squamous cell carcinoma. In this study, we investigated the associations between Krüppel-like factor 4 expression and clinical parameters of oral cancer using immunohistochemical assays in 215 surgical specimens. Compared with positive nuclear Krüppel-like factor 4 expression, we observed that negative nuclear Krüppel-like factor 4 expression was significantly associated with an advanced cancer stage (P = .046), a high tumor recurrence rate (P = .009), and a worse 3-year survival rate in patients with oral cancer (P = .046). Nuclear expression of Krüppel-like factor 4 was shown to have an inverse relationship with Ki67 expression (P = .046). Patients with negative nuclear expression of Krüppel-like factor 4 had significantly worse overall survival rates as defined by the log-rank test (P = .014). Patients with oral cancer with negative nuclear Krüppel-like factor 4 expression in tumor cells had poor prognoses and a 2.5-fold higher death risk. Compared with disease stage (P = .025), negative nuclear Krüppel-like factor 4 expression (P = .006) was an independent prognostic factor. Our results revealed that the loss of nuclear expression of Krüppel-like factor 4 is significantly associated with aggressive clinical manifestations and might be an adverse survival factor.