Overexpression of mitogen-activated protein kinase kinase 4 and nuclear factor-kappaB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis.
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.
Huang
Chuang
C
Department of Otolaryngology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China.
Huang
Kun
K
Wang
Chi
C
Jiang
Zhen-Dong
ZD
Li
Xing-Xing
XX
Wang
Hong-Peng
HP
Chen
Hong-Yan
HY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008207:Lymphatic Metastasis; D048670:MAP Kinase Kinase 4 / Q000032:analysis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis* / Q000235:genetics; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human