Jin Guo-Hua, Xu Wei, Shi Yang, Wang Li-Bo
Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Laboratory, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2016 Oct;12(4):2345-2350. doi: 10.3892/ol.2016.4976. Epub 2016 Aug 8.
Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database. Two groups of differentially expressed genes (DEGs) were identified using limma package in R language. The criterion for GSE56807 was a false discovery rate of <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets were screened out. Subsequently, pathway enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery software (P<0.1; gene count ≥2). In addition, the protein-protein interactions (PPIs) among the overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins, Biomolecular Interaction Network Database and Human Protein Reference Database. Finally, a PPI network was visualized using Cytoscape software. A total of 137 overlapped DEGs were obtained, and DEGs with opposite regulation directions in the two datasets were significantly enriched in focal adhesion and leukocyte transendothelial migration. Subsequently, a PPI network of overlapped DEGs was constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich protein 1 (), thrombospondin 1 (), myosin light chain 9 (), filamin A (), actinin alpha 1 (), vinculin (), laminin subunit gamma 2 () and claudin 1 ()] were upregulated in GC tissues and downregulated in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects by suppressing the expression of , , , , , , and , and inhibiting leukocyte transendothelial migration and focal adhesion. However, relevant experiments are required to confirm the conclusion of the present study.
胃癌（GC）是一种常见的癌症，目前仍无法治愈，因此需要替代治疗方法。塞来昔布是一种靶向环氧化酶-2的非甾体抗炎药，具有抗癌作用。本研究旨在使用生物信息学方法研究塞来昔布的抗GC机制。从基因表达综合数据库下载基因表达数据集GSE56807（GC组织和正常胃组织）和GSE54657（塞来昔布处理和未处理的人GC上皮AGS细胞）。使用R语言中的limma软件包鉴定两组差异表达基因（DEG）。GSE56807的标准是错误发现率<0.05，而GSE54657的标准是P<0.01。筛选出两个数据集中重叠的DEG。随后，使用注释、可视化和综合发现数据库软件进行通路富集分析（P<0.1；基因计数≥2）。此外，基于IntAct、相互作用蛋白质数据库、生物分子相互作用网络数据库和人类蛋白质参考数据库获得重叠DEG之间的蛋白质-蛋白质相互作用（PPI）。最后，使用Cytoscape软件可视化PPI网络。共获得137个重叠的DEG，两个数据集中调控方向相反的DEG在粘着斑和白细胞跨内皮迁移中显著富集。随后，构建了重叠DEG的PPI网络。综合来看，共有8个关键DEG[富含半胱氨酸和甘氨酸蛋白1（）、血小板反应蛋白1（）、肌球蛋白轻链9（）、细丝蛋白A（）、辅肌动蛋白α1（）、纽蛋白（）、层粘连蛋白亚基γ2（）和紧密连接蛋白1（）]在GC组织中上调，在塞来昔布处理的细胞中下调。总之，塞来昔布可能通过抑制、、、、、、和的表达，抑制白细胞跨内皮迁移和粘着斑，从而发挥抗GC作用。然而，需要相关实验来证实本研究的结论。
