Elevated DKK1 expression is an independent unfavorable prognostic indicator of survival in head and neck squamous cell carcinoma
Received 13 June 2018
Accepted for publication 3 September 2018
Published 30 October 2018 Volume 2018:10 Pages 5083—5089
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 4
Editor who approved publication: Dr Antonella D'Anneo
Haihe Gao,1 Lisha Li,2 Mang Xiao,3 Yongwei Guo,4 Yi Shen,5,6 Lixin Cheng,5 Ming Tang5
1Department of Otolaryngology Head and Neck Surgery, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2Department of Nursing, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo 315041, People’s Republic of China; 3Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Ophthalmology, University of Cologne, 50937, Cologne, Germany; 5Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, People’s Republic of China; 6Department of Otolaryngology Head and Neck Surgery, School of Medicine, Ningbo University, Ningbo 315211, People’s Republic of China
Purpose: DKK1 is an antagonist of the Wnt signaling pathway that has various roles in human physiology. Notably, aberrant DKK1 expression is observed in several cancers. In this retrospective study, we assessed the association between DKK1 expression levels and head and neck squamous cell carcinoma (HNSCC) and its prognostic value.
Materials and methods: Using RNA-seq data from HNSCC tumors (N=520) and adjacent normal tissue (N=44) in The Cancer Genome Atlas, we evaluated DKK1 expression levels. Additionally, we evaluated the association of DKK1 expression levels and pathophysiological features of patients with HNSCC and the value of DKK1 expression for prediction of overall survival (OS). We also explored the correlation between DKK1 expression and methylation of its promoter in HNSCC.
Results: DKK1 expression was significantly upregulated in HNSCC compared with normal tissues. Moreover, DKK1 expression was significantly associated with smoking, alcohol abuse, sex, human papillomavirus status, tumor site, tumor invasion, and pathologic stage in HNSCC patients. Kaplan–Meier curves showed that high DKK1 expression was correlated with inferior OS. In addition, univariate and multivariate analyses showed that elevated DKK1 expression was an independent prognostic factor for poor OS (HR: 1.85, 95% CI: 1.31–2.62, P<0.001). Regression analysis identified a strong negative correlation between DKK1 expression and methylation of its promoter.
Conclusion: These findings support the hypothesis that elevated DKK1 expression is modulated via methylation of its promoter and indicate that DKK1 expression is a highly informative prognostic biomarker for patients with HNSCC.
Keywords: HNSCC, DKK1, overall survival, prognosis, methylation
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