J Cancer 2019; 10(22):5413-5426. doi:10.7150/jca.34261

Research Paper

EP300 as an oncogene correlates with poor prognosis in esophageal squamous carcinoma

Yanghui Bi1,12,#, Pengzhou Kong1,#, Ling Zhang1,2,#, Heyang Cui1,#, Xiaoqin Xu1,3,#, Feiyun Chang4,#, Ting Yan1, Jiayi Li5, Caixia Cheng1,6, Bin Song1,7, Xia Niu1, Xiangchen Liu1, Xue Liu1, Enwei Xu1,8, Xiaoling Hu1,9, Yu Qian1, Fang Wang1, Hongyi Li1, Yanchun Ma1, Jian Yang1, Yiqian Liu1, Yuanfang Zhai1, Yi Wang1, Yingchun Zhang1, Haiyan Liu1,10, Jing Liu1,11, Jintao Wang12,✉, Yongping Cui1, Xiaolong Cheng1,13,✉

1. Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
2. Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R.China
3. Department of Etiology, Shanxi Cancer Hospital, Taiyuan, Shanxi030001, P.R.China
4. Department of General Surgery, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001, P.R. China
5. Anglo-Chinese School (Independent), Singapore
6. Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
7. Department of Oncology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
8. Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030001, P.R. China
9. Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
10. Department of Nuclear Medicine, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
11. Department of General Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
12. Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, P.R. China.
13. Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
#These authors contributed equally to this work

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:
Bi Y, Kong P, Zhang L, Cui H, Xu X, Chang F, Yan T, Li J, Cheng C, Song B, Niu X, Liu X, Liu X, Xu E, Hu X, Qian Y, Wang F, Li H, Ma Y, Yang J, Liu Y, Zhai Y, Wang Y, Zhang Y, Liu H, Liu J, Wang J, Cui Y, Cheng X. EP300 as an oncogene correlates with poor prognosis in esophageal squamous carcinoma. J Cancer 2019; 10(22):5413-5426. doi:10.7150/jca.34261. Available from http://www.jcancer.org/v10p5413.htm

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Abstract

E1A Binding Protein P300 (EP300) is one of the mutations of genes involved in histone modifications in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance, potential function and mechanisms have remained elusive.

Methods: Genomic sequencing datas from 325 esophageal squamous cell carcinoma (ESCC) cases were integrated and screened a series of frequently mutated histone modifier genes. EP300 was selected to further analyze its clinical significance, function and RNA-sequencing was performed to explore its potential mechanism.

Results: Of 35 histone modifier genes, EP300 was not only a significantly mutated gene but also a frequently mutated gene with a mutation frequency of more than 10% in ESCC. EP300 mutation was associated with tumor grade, pathological T stage and lymph node metastasis, predicting a shorter cumulative survival status. Immunohistochemical analysis showed that EP300 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with poor survival of ESCC patients. Moreover, we found that EP300 knockdown led to inhibition of cell proliferation, colony formation, migration and invasion. RNA-sequencing showed EP300 knockdown led to a significant change of genes expression associated with angiogenesis, hypoxia and epithelial-to-mesenchymal transition (EMT).

Conclusions: Taken together, our study identified a novel role and mechanism of EP300 in ESCC and provided epigenetic therapeutic strategies for the treatment of ESCC.

Keywords: EP300, ESCC, prognosis, angiogenesis, EMT