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Prognostic significance of preoperative IKBKE expression in esophageal squamous cell carcinoma

Authors Yang WJ, Qu Y, Tan BX, Jia YB, Wang NN, Hu P, Wang JB

Received 12 November 2017

Accepted for publication 18 January 2018

Published 7 March 2018 Volume 2018:11 Pages 1305—1314

DOI https://doi.org/10.2147/OTT.S156818

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza


Wenjing Yang, Yan Qu, Bingxu Tan, Yibin Jia, Nana Wang, Peng Hu*, Jianbo Wang*

Department of Radiation, Qilu Hospital of Shandong University, Jinan, People’s Republic of China

*These authors contributed equally to this work

Purpose: IκB kinase epsilon (IKBKE; IKKε), a member of the nuclear factor-κB kinase inhibitor family, is upregulated in several human cancers, including breast cancer, prostate cancer, and ovarian cancer. Esophageal squamous cell carcinoma (ESCC) is one of the most common and most aggressively malignant cancers with dismal prognosis. However, the state of IKBKE expression in ESCC is still unknown and its potential value remains unexplored.
Patients and methods: IKBKE protein expression was evaluated by immunohistochemistry in 118 paraffin specimens of ESCC treated by curative surgery. All patients were regularly followed up by telephone over 3 years after surgery. The chi-square test, Kaplan–Meier method, and Cox proportional hazard regression model were used to analyze the relationship of IKBKE expression, clinicopathological characteristics, and prognostic value for ESCC.
Results: IKBKE expression was 61.9% (73/118) in paraffin-embedded archived ESCC. Its expression was significantly associated with tumor differentiation grade (p=0.045) and advanced TNM (pathologic tumor node metastasis) stages (p=0.023). In univariate analysis, IKBKE expression was closely associated with decreased 3-year disease-free survival (HR 1.804, 95% CI 1.076–3.027; p=0.023) and overall survival (HR 2.118, 95% CI 1.189–3.773; p=0.009). Meanwhile, in multivariate analysis it was identified as an independent prognostic factor for 3-year disease-free survival (HR 1.777, 95% CI 1.034–3.054; p=0.037) and overall survival (HR 2.078, 95% CI 1.138–3.796; p=0.017).
Conclusion: Our data indicated for the first time that IKKε expression is a highly recurrent event in ESCC and could play a pivotal role in the evaluation of prognosis. IKBKE upregulation is negatively associated with disease-free survival and overall survival. Therefore, IKBKE could serve as a prognostic variable and potential therapeutic target for this malignancy.

Keywords:
IKBKE, esophageal squamous cell carcinoma, biomarker, prognosis, immunohistochemistry
 

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