ONECUT2 基因在人胃癌中的表达及其临床意义

目的：探讨ONECUT2（one cut homeobox 2，OC-2）基因在人胃癌组织中的表达水平及其临床意义。方法：基于生物信息学技术全面检索Oncomine、GEPIA、CCLE、EBI 数据库，分析OC-2 在胃癌和其他种类肿瘤中的表达水平，用Kmplot 数据库验证其表达水平与胃癌患者预后的关系，用STRING数据库构建蛋白互作网络（protein protein interaction network，PPI network），分析与胃癌相关的OC-2 共表达基因。结果：在OC-2 差异表达的不同种类肿瘤中，其表达水平一般上调。在胃癌组织和细胞中OC-2 表达水平均显著升高（均P<0.05），且可能与组织分型和肿瘤分期无关（均P>0.05）。OC-2 表达水平与胃癌患者的预后有关，OC-2 低表达组胃癌患者的中位总生存期和中位无病生存期均显著高于高表达组（40.0 vs 26.5 个月，26.2 vs 16.1 个月；均P<0.01）。筛查获得了15 个OC-2 的共表达基因；构建的PPI 网络预测了30 个功能蛋白与OC-2 蛋白相互作用，其中有11 个蛋白基因也与胃癌的发生发展有关，Pearson 相关分析后得出4个与OC-2密切正相关的蛋白基因：PDX1（R=0.49）、CREB1（R=0.31）、MAPK1（R=0.26）、CTSS（R=0.25）。结论：OC-2 在胃癌发生发展及侵袭转移过程中可能起重要的作用，有望成为胃癌诊治和判断预后的重要指标和新的筛查靶点。

Expression and clinical significance of ONECUT2 gene in human gastric cancer

Objective: To investigate the expression of one cut homeobox 2, OC-2 (ONECUT2) gene in human gastric cancer and its clinical significance. Methods: Based on bioinformatics technology, Oncomine, GEPIA, CCLE and EBI databases were searched to analyze the expression level of OC-2 in gastric cancer (GC) and other tumors. Kmplot database was used to verify the correlation between OC-2 expression and the prognosis of gastric cancer patients. STRING database was used to construct proteinprotein interaction network (PPI network), and the co-expressed genes of OC-2 related with gastric cancer were also analyzed.Results: The expression of OC-2 was generally up-regulated in different kinds of tumors with differential OC-2 expression. The expression level of OC-2 increased significantly in gastric cancer tissues and cells (all P<0.05) and might be irrelevant with tissue type and tumor stage (all P>0.05). The expression level of OC-2 was correlated with prognosis of gastric cancer patients. The median overall survival (40.0 vs 26.5 months) and median disease-free survival (26.2 vs 16.1 months) of gastric cancer patients with low OC-2 expression was significantly longer than those patients with high expression (both P<0.01). Fifteen co-expressed genes of OC-2 were obtained; the PPI network predicted 30 functional proteins interacting with OC-2, among which 11 proteins were also related to the occurrence and development of gastric cancer. After Pearson correlation analysis, 4 proteins that closely and positively related to OC-2 were identified: PDX1 (R=0.49), CREB1 (R=0.31), MAPK1 (R=0.26) and CTSS (R=0.25). Conclusion: OC-2 may play an important role in the occurrence and development, as well as invasion and metastasis of gastric cancer, which is expected to become a new target for the diagnosis and treatment of gastric cancer, and also an important indicator for the prognosis prediction of gastric cancer patients.