Int J Med Sci 2020; 17(11):1598-1609. doi:10.7150/ijms.46809

Research Paper

Overexpression of ATAD2 indicates Poor Prognosis in Oral Squamous Cell Carcinoma

Xiao-Long Wang1,3, Shuo Wang1, Zhi-Zhong Wu1, Qi-Chao Yang1, Hao Li1, Hong-Gang Xiong1, Shu-Cheng Wan1, Zhi-Jun Sun1,2✉

1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
2. Department of Oral Maxillofacial-Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
3. Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wang XL, Wang S, Wu ZZ, Yang QC, Li H, Xiong HG, Wan SC, Sun ZJ. Overexpression of ATAD2 indicates Poor Prognosis in Oral Squamous Cell Carcinoma. Int J Med Sci 2020; 17(11):1598-1609. doi:10.7150/ijms.46809. Available from http://www.medsci.org/v17p1598.htm

File import instruction

Abstract

ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of malignancies and can promote the proliferation of tumor cells and inhibit their differentiation. However, the expression of ATAD2 and its related mechanism in oral squamous cell carcinoma (OSCC) are still unknown. Immunohistochemical staining of ATAD2, cancer stem cells (CSCs) markers and immune checkpoint molecules was conducted on human OSCC specimens to determine the expression levels of these proteins and their correlations with the clinicopathological characteristics of ATAD2 in OSCC. Moreover, the role of ATAD2 in cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) were assessed by silencing ATAD2 in vitro. Immunohistochemical analysis revealed that ATAD2 expression in OSCC tissues was markedly higher than that in adjacent dysplastic tissues and normal mucosal tissues. Overexpression of ATAD2 was related to poor overall survival in OSCC patients. In addition, the protein expression of ATAD2 was notably correlated with the expression of B7-H4, PD-L1, CMTM6, Slug and ALDH1 in human OSCC. ATAD2 knockdown arrested the cell cycle, promoted the apoptosis, and inhibited the proliferation, migration, and EMT of OSCC cells. In conclusion, these findings revealed that ATAD2 is highly expressed in OSCC and can act as a poor prognostic indicator.

Keywords: ATAD2, oral squamous cell carcinoma, prognosis, proliferation, apoptosis, epithelial-mesenchymal transition