JMJD3 expression is an independent prognosticator in patients with esophageal squamous cell carcinoma

被引:20
作者
Li, Shau-Hsuan [1 ,2 ]
Lu, Hung-I [2 ,3 ]
Chen, Yen-Hao [1 ,2 ]
Lo, Chien-Ming [2 ,3 ]
Huang, Wan-Ting [2 ,4 ]
Tien, Wan-Yu [1 ,2 ]
Lan, Ya-Chun [1 ,2 ]
Tsai, Hsin-Ting [5 ,6 ]
Chen, Chang-Han [5 ,6 ,7 ,8 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Dept Hematol Oncol, Kaohsiung, Taiwan
[2] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan
[3] Kaohsiung Chang Gung Mem Hosp, Dept Thorac & Cardiovasc Surg, Kaohsiung, Taiwan
[4] Kaohsiung Chang Gung Mem Hosp, Dept Pathol, Kaohsiung, Taiwan
[5] Natl Chi Nan Univ, Dept Appl Chem, Nantou, Taiwan
[6] Natl Chi Nan Univ, Grad Inst Biomed & Biomed Technol, Nantou, Taiwan
[7] Sun Yat Sen Univ, Guangdong Inst Gastroenterol, Guangzhou, Guangdong, Peoples R China
[8] Sun Yat Sen Univ, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou, Guangdong, Peoples R China
关键词
HISTONE DEMETHYLASE JMJD3; CANCER; CONTRIBUTES; ACTIVATION; SENESCENCE; INK4A/ARF; UTX;
D O I
10.1016/j.surg.2018.11.015
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: The Jumonji-domain containing 3 has diverse roles in multiple cancers. Here, we investigated its prognostic significance in esophageal squamous cell carcinoma. Methods: By using immunohistochemistry, the Jumonji-domain containing 3 expression was examined in 109 surgically resected esophageal squamous cell carcinomas and correlated with treatment outcome. The functional role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells was determined by Jumonji-domain containing 3-mediated small interfering ribonucleic acid. Results: Univariate analysis showed that Jumonji-domain containing 3 overexpression was associated with inferior overall survival (P =.004) and disease-free survival (P=.002). In a multivariate comparison, Jumonji-domain containing 3 overexpression remained independently associated with worse overall survival (P=.017, hazard ratio =1.898) and disease-free survival (P=.011, hazard ratio =1.901). The 5-year overall and disease-free survival rates were 66% and 58% in patients with a low expression of Jumonji-domain containing 3 and 34% and 27% in patients with overexpression of Jumonji-domain containing 3. Silencing Jumonji-domain containing 3 in esophageal squamous cell carcinoma cells inhibited cell growth rate and bromodeoxyuridine incorporation ability. In contrast, a gain of function of Jumonji-domain containing 3 promoted esophageal squamous cell carcinoma cell proliferation. Furthermore, Jumonji-domain containing 3 expression contributes to Ras/MEK pathway. Conclusion: Jumonji-domain containing 3 overexpression was independently associated with poor prognosis in patients with esophageal squamous cell carcinoma. In vitro, Jumonji-domain containing 3 expression regulated esophageal squamous cell carcinoma cell growth. These results may further elucidate the role of Jumonji-domain containing 3 in esophageal squamous cell carcinoma and provide a potential new therapeutic approach for patients with esophageal squamous cell carcinoma. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:946 / 952
页数:7
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