Clinicopathological significance and prognostic implication of nuclear factor-κB activation in colorectal cancer.

OBJECTIVE

The aim of the present study was to evaluate the clinicopathological significance of phosphorylated nuclear factor-κB (pNF-κB) expression, and its impact on epithelial-mesenchymal transition and angiogenesis in colorectal cancer (CRC).

METHODS

We carried out immunohistochemistry of pNF-κB on 261 human CRC tissues, and evaluated nuclear expression, regardless of cytoplasmic expression. We also investigated the correlation between pNF-κB expression and clinicopathological characteristics, survival, and epithelial-mesenchymal transition and angiogenesis-related markers in CRC.

RESULTS

pNF-κB was expressed in the nuclei of 164 of the 261 CRC tissues (62.8%). Furthermore, pNF-κB was significantly correlated with frequent perineural invasion, lymph node metastasis, and higher pTNM stage. However, there was no significant correlation between pNF-κB expression and other clinicopathological parameters. Among the epithelial-mesenchymal transition markers examined, SNAIL expression was significantly correlated with pNF-κB expression (P =  0.001) but E-cadherin expression was not. CRC with pNF-κB expression had significantly higher SIRT1 expression levels and hypoxia-inducible factor-1α expression levels than CRC without pNF-κB expression (P <  0.001 and P <  0.001, respectively). However, there was no correlation between the expression levels of pNF-κB and VEGF. pNF-κB expression was significantly correlated with worse overall and recurrence-free survival rates (P <  0.001 and P <  0.001, respectively).

CONCLUSION

pNF-κB expression was significantly correlated with aggressive tumor behaviors and worse survival rates. Furthermore, pNF-κB expression may affect tumor invasion and progression through SNAIL-related epithelial-mesenchymal transition and SIRT1- and hypoxia-inducible factor-1α-induced angiogenesis.