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

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-alpha-tubulin as well as common epithelial-mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and beta-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-alpha-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.

Automated summary

NEK9 plays a critical role in microtubule polymerization, chromosome alignment, and mitosis in colon cancer. Immunohistochemistry analysis of 138 patients with pT3 colon cancers revealed that NEK9 expression is associated with distant metastasis and is an independent predictive factor. Positive correlations were observed between NEK9 and EG5 or acetyl-alpha-tubulin, confirming the role of the NEK9-EG5 axis in colon cancer.