Hashimoto Tadayoshi, Kurokawa Yukinori, Wada Noriko, Takahashi Tsuyoshi, Miyazaki Yasuhiro, Tanaka Koji, Makino Tomoki, Yamasaki Makoto, Nakajima Kiyokazu, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Oncol Lett. 2020 Jan;19(1):1066-1073. doi: 10.3892/ol.2019.11138. Epub 2019 Nov 21.
Chromodomain helicase DNA-binding 5 (), which is a member of the family, has been identified as a tumor suppressor gene in a variety of malignancies. The aim of the current study was to clarify the clinical significance of CHD5 expression in gastric cancer. CHD5 expression was evaluated using immunohistochemistry (IHC) in 154 specimens resected from patients with gastric cancer from January 2011 to December 2013, and assessed its relationships with clinicopathological characteristics and survival. cell proliferation, invasion, and migration assays and western blotting analysis were performed to clarify the role of CHD5 in human gastric cancer cell lines. Of a total of 154 patients, 57 (37.0%) exhibited low CHD5 expression, which was significantly associated with positive lymphatic invasion (P=0.032), advanced pT status (P=0.011), and advanced pStage (P=0.014). Overall survival (OS) in patients with low CHD5 expression was significantly worse compared with patients with high CHD5 expression (hazard ratio, 1.96; 95% confidence interval, 1.09-3.45; log-rank P=0.023). Cox multivariate analysis for OS revealed that CHD5 expression was an independent prognostic factor with age and pN status. , the upregulation of CHD5 in gastric cancer cells with low CHD5 expression significantly decreased cell proliferation, migration and invasion. CHD5 was associated with the regulation of multiple cancer-related targets, including p53 and enhancer of zeste homolog 2 (EZH2) in western blotting analysis. In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer.
染色质结构域解旋酶DNA结合蛋白5(CHD5)是CHD家族的成员之一,已被确定为多种恶性肿瘤中的肿瘤抑制基因。本研究的目的是阐明CHD5表达在胃癌中的临床意义。使用免疫组织化学(IHC)对2011年1月至2013年12月间从胃癌患者切除的154个标本进行CHD5表达评估,并评估其与临床病理特征和生存的关系。进行细胞增殖、侵袭和迁移试验以及蛋白质印迹分析,以阐明CHD5在人胃癌细胞系中的作用。在总共154例患者中,57例(37.0%)表现出低CHD5表达,这与阳性淋巴管浸润(P=0.032)、进展期pT状态(P=0.011)和进展期p分期(P=0.014)显著相关。CHD5低表达患者的总生存期(OS)与CHD5高表达患者相比显著更差(风险比,1.96;95%置信区间,1.09 - 3.45;对数秩P=0.023)。对OS的Cox多因素分析显示,CHD5表达与年龄和pN状态一样是独立的预后因素。此外,CHD5低表达的胃癌细胞中CHD5的上调显著降低了细胞增殖、迁移和侵袭。在蛋白质印迹分析中,CHD5与包括p53和zeste同源物2增强子(EZH2)在内的多个癌症相关靶点的调节有关。总之,由于CHD5调节多个癌症相关靶点,其表达可能是胃癌患者有用的预后生物标志物。