IKK epsilon and TBK1 expression in gastric cancer

Abstract

Inhibitor of kappa B kinase epsilon (IKK epsilon) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKK epsilon and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKK epsilon ad TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKK epsilon and TBK1 in gastric cancer and their role in prognosis have not been studied. To investigate overexpression of the IKK epsilon and TBK1 proteins in gastric cancer and their relationship with clinicopathologic factors, we performed immunohistochemical staining using a tissue microarray. Tissue microarray samples were obtained from 1,107 gastric cancer patients who underwent R0 gastrectomy with extensive lymph node dissection and adjuvant chemotherapy. We identified expression of IKK epsilon in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKe and TBK1 was identified in 1.5% of cases. Co-expression of IKK epsilon and TBK1 was associated with differentiated intestinal histology and earlier T stage. In a multivariate binary logistic regression model, intestinal histologic type by Lauren classification and early AJCC stage were significant predictors for expression of IKK epsilon and TBK1 proteins in gastric cancer. Changes in IKK epsilon and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKK epsilon and TBK1 should be considered in selected patients with intestinal-type gastric cancer. In conclusion, this is the first large-scale study investigating the relationships between expression of IKK epsilon and TBK1 and clinicopathologic features of gastric cancer. The role of IKK epsilon and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation