Overexpression of ZRF1 is related to tumor malignant potential and a poor outcome of gastric carcinoma
Overexpression of ZRF1 is related to tumor malignant potential and a poor outcome of gastric carcinoma
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DOI：
10.1093/carcin/bgx139
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发表时间：
2018-02-01
期刊：
影响因子：
4.7
通讯作者：
Otsuji, Eigo
中科院分区：
文献类型：
--
作者：
Imamura, Taisuke;Komatsu, Shuhei;Otsuji, Eigo
Zuotin-related factor 1（ZRF 1）是一种新近发现的参与转录调控的表观遗传因子，在多种恶性肿瘤中高度表达，但它是否在胃癌中发挥作用尚不清楚。在这项研究中，我们研究了ZRF 1是否通过其在GC中的激活/过表达作为促癌基因。我们分析了五个GC细胞系和133原发性肿瘤，已在我院2001年和2003年之间治愈切除。ZRF 1在胃癌细胞系中的表达率为80.0%（4/5），在133例胃癌中的表达率为39.1%（52/133），与胃癌的分化程度、静脉浸润、淋巴结浸润、肿瘤分期及复发率密切相关。ZRF 1过表达的肿瘤的生存率比不表达的肿瘤差（P < 0.01，对数秩检验）。在多变量分析中，ZRF 1阳性与更差的预后独立相关（P < 0.01;风险比4.92; 95%置信区间：1.6-21.1）。在ZRF 1过表达的GC细胞中，使用特异性siRNA敲低ZRF 1抑制细胞增殖、迁移和侵袭，并以p53依赖的方式诱导细胞凋亡。这些发现表明，ZRF 1通过其过表达在肿瘤恶性潜能中起着至关重要的作用，并突出了其作为胃癌预后因子和潜在治疗靶点的有用性。
Zuotin-related factor 1 (ZRF1) is a recently characterized epigenetic factor involved in transcriptional regulation and is highly overexpressed in several malignancies, but it is not known whether it plays a role in gastric cancer (GC). In this study, we investigated whether ZRF1 acts as a cancer-promoting gene through its activation/overexpression in GC. We analyzed five GC cell lines and 133 primary tumors, which had been curatively resected in our hospital between 2001 and 2003. Overexpression of ZRF1 was detected in GC cell lines (four out of five lines, 80.0%) and was detected in primary tumor samples of GC (52 out of 133 cases, 39.1%) and significantly correlated with differentiated histological type, venous invasion, lymphatic invasion, advanced stage and a higher recurrence rate. ZRF1-overexpressing tumors had a worse survival rate than those with non-expressing tumors (P < 0.01, log-rank test). ZRF1 positivity was independently associated with a worse outcome in the multivariate analysis (P < 0.01; hazard ratio 4.92; 95% confidence interval: 1.6-21.1). In ZRF1-overexpressing GC cells, knockdown of ZRF1 using specific siRNAs inhibited the cell proliferation, migration and invasion and induced apoptosis in a p53-dependent manner. These findings suggest that ZRF1 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.