Overexpression of mitogen-activated protein kinase kinase 4 and nuclear factor-kappaB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis

Abstract

This study aimed to investigate the expression and clinical significance of mitogen-activated protein kinase kinase 4 MKK4 and nuclear factor-kappaB (NF-kappaB) in patients with laryngeal squamous cell carcinoma (LSCC). We used immunohistochemistry (IHC) to examine the expression of MKK4 and NF-kappaB in 78 LSCCs and their adjacent normal tissues. To clarify the validity of MKK4 and NF-kappaB as determined by the IHC analysis, RT-PCR was performed on 21 tissues randomly selected from the 78 LSCCs. The positive expression rates of MKK4 and NF-kappaB in patients with LSCC were 67.9% (53/78) and 60.3% (47/78) respectively, which were significantly higher than those in the adjacent normal tissue (both P<0.01). The positive expression of MKK4 and NF-kappaB tended to be associated positively with lymph node metastasis (both P<0.01) as well as T stage (both P<0.01). The Spearman analysis indicated that the expression level of MKK4 was positively correlated with that of NF-kappaB significantly (rs=0.368, P<0.01). Overall survival curves estimated by Kaplan-Meier showed that tumor patients with low MKK4 and NF-kappaB expression in their tumor cells survive significantly longer than patients with high MKK4 and NF-kappaB levels (P=0.027, and P<0.01, respectively). In addition, multivariate Cox regression analysis showed that N stage, T stage and NF-kappaB expression are significant independent prognostic factors for overall survival (P<0.01, P=0.014, and P=0.027, respectively). These findings suggested that the expression of MKK4 and NF-kappaB may be considered as a useful prognostic marker of LSCC after surgical resection.