Shau-Hsuan Li1, Hung-I Lu2, Yen-Hao Chen1, Chien-Ming Lo2, Wan-Ting Huang3, Wan-Yu Tien1, Ya-Chun Lan1, Hsin-Ting Tsai4, Chang-Han Chen5. 1. Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China. 2. Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 3. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 4. Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, Taiwan. 5. Department of Applied Chemistry, and Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, Taiwan; Guangdong Institute of Gastroenterology, and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sun Yat-sen University, Guangzhou, China. Electronic address: chenchhan@mail.sysu.edu.cn.
Abstract
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.
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.