Upregulation of Krüppel-Like Factor 4 (KLF-4) Expression as a Potential Tumor Progression Gene Product in Non-Hodgkin's Lymphoma.

Abstract 5022

Krüppel-like factor 4 (KLF-4) is highly expressed in epithelial tissues such as the gut and skin. Several studies based on clinical evidence suggest that KLF-4 functions as a tumor suppressor in cancers of the colon, bladder, stomach and in leukemia. In contrast, KLF-4 expression is increased in primary breast ductal carcinomas and in oral dermal squamous cell carcinomas, suggesting that KLF-4 is important in tumor development and progression. However, KLF-4 expression in lymphomas has not been investigated. Our preliminary studies have examined KLF-4 expression in lymphoma cell lines and a TMA containing fresh tissues derived from patients with several types of lymphoma. There was a significantly higher expression of KLF-4 in Burkitt's lymphoma compared with other lymphomas such as follicular or DLBCL. These findings suggest that KLF-4 may be considered as a new biomarker in Non-Hodgkin's lymphoma (NHL). Further analyses based on the clinical outcome revealed that KLF-4 protein expression was significantly associated with poor patient's survival. The increased KLF-4 expression was associated with an inferior survival duration (P= 0.002). The survival for 12 patients who had a tumor with weak KLF-4 expression and 13 patients with negative KLF-4 expression was significantly longer than that for the 30 patients with strong KLF-4 expression (P< 0.001). Other variables that affected survival in univariate analyses included stages and completeness of resection were shown to have a statistically significant effect on survival (P=0.001), however age or sex did not have a statistically significant effect on survival. These data provide the first clinical and causal evidences that alterations of KLF-4 expression can play a critical role in the development and progression of NHL.