Overexpression of the NEK9-EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer

Abstract

NEK9 is a key player in the NEK9–EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial–mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and β-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis (P = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P = 0.007) or lymphovascular invasion (HR = 2.090, P = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P = 0.007; r = 0.181 and P = 0.038, respectively) and concordant overexpression of the NEK9–EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9–EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.