Oncotarget

Research Papers:

IKKε and TBK1 expression in gastric cancer

Seung Eun Lee, Mineui Hong, Junhun Cho, Jeeyun Lee _ and Kyoung-Mee Kim

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Oncotarget. 2017; 8:16233-16242. https://doi.org/10.18632/oncotarget.9069

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Abstract

Seung Eun Lee1,*, Mineui Hong2,*, Junhun Cho3, Jeeyun Lee4, Kyoung-Mee Kim3

1Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea

2Department of Pathology, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea

3Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Jeeyun Lee, e-mail: jyunlee@skku.edu

Kyoung-Mee Kim, e-mail: kkmkys@skku.edu

Keywords: IKKε, TBK1, gastric, cancer, therapy

Received: September 22, 2015    Accepted: March 31, 2016    Published: April 28, 2016

ABSTRACT

Inhibitor of kappa B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKKε and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKKε and TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKKε and TBK1 in gastric cancer and their role in prognosis have not been studied.

To investigate overexpression of the IKKε 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 IKKε in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKε and TBK1 was identified in 1.5% of cases. Co-expression of IKKε 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 IKKε and TBK1 proteins in gastric cancer. Changes in IKKε and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKKε 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 IKKε and TBK1 and clinicopathologic features of gastric cancer. The role of IKKε and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation.


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