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WDR5 Promotes Proliferation and Correlates with Poor Prognosis in Oesophageal Squamous Cell Carcinoma

Authors Huang D, Chen X, Chen X, Qu Y, Wang Y, Yang Y, Cheng Y

Received 15 October 2019

Accepted for publication 11 September 2020

Published 15 October 2020 Volume 2020:13 Pages 10525—10534

DOI https://doi.org/10.2147/OTT.S234773

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Federico Perche


Di Huang,1 Xue Chen,1 Xuan Chen,1 Yan Qu,1 Yuanyuan Wang,2 Yafei Yang,3 Yufeng Cheng1

1Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Oncology, People’s Hospital of Linyi County, Dezhou, Shandong 251500, People’s Republic of China; 3Department of Hepatobiliary Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China

Correspondence: Yufeng Cheng Department of Radiation Oncology
Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 West Wenhua Road, Jinan, Shandong 250012, People’s Republic of China
, Email qiluchengyufeng@126.com

Background: The WD40 protein family member WD repeat domain 5 (WDR5) plays significant roles in the tumorigenesis and development of multiple organ tumours. However, the correlation between WDR5 expression and oesophageal squamous cell carcinoma (ESCC) has not been elucidated.
Methods: WDR5 mRNA expression data were acquired from The Cancer Genome Atlas (TCGA) database, and the expression and prognostic potential of WDR5 were assessed by immunohistochemistry (IHC) and Western blot. The cell counting kit-8 (CCK-8), colony formation assay and cell cycle evaluation were performed to verify the WDR5 function in vitro. The xenograft model was used to verify WDR5 function in vivo.
Results: The mRNA and protein expression levels of WDR5 were significantly upregulated in ESCC tissues compared with expression in adjacent normal tissues. Kaplan–Meier analysis showed that high WDR5 expression in ESCC patients was associated with poor overall survival (P=0.004). Multivariate analysis revealed that WDR5 overexpression emerged as an independent predictor of poor overall survival (P=0.013) in ESCC. The in vitro and in vivo experiments revealed that downregulation of WDR5 expression blocked cell proliferation of ESCC. Mechanistically, we found that WDR5 may influence ESCC proliferation by targeting the PI3K/AKT/mTOR signalling pathway.
Conclusion: Our data demonstrate that overexpression of WDR5 was associated with poor prognosis in patients with ESCC and that WDR5 may act as a potential novel prognostic biomarker for ESCC.

Keywords: WDR5, oesophageal squamous cell carcinoma, prognosis, proliferation

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