Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis.
Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis.
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利用生物信息学分析确定四跨膜蛋白家族是胃癌中检测到的中心基因
DOI：
10.3892/mmr.2018.9360
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发表时间：
2018-10
影响因子：
3.4
通讯作者：
Qiu W
中科院分区：
文献类型：
--
作者：
Qi W;Sun L;Liu N;Zhao S;Lv J;Qiu W
胃癌在过去十年中已成为一种严重的疾病。它在四种最常见的癌症类型中具有第二高的死亡率，每年导致约700，000人死亡。先前的研究试图阐明胃癌的潜在生物学机制。本研究的目的是获得有用的生物标志物，并提高在基因水平上的胃癌机制的理解。本研究使用生物信息学分析来鉴定从GSE 54129数据集获得的1，829个差异表达基因（DEG）。使用来自检索相互作用基因数据库的搜索工具的蛋白质-蛋白质相互作用信息，使用Cytoscape软件构建胃癌的疾病模块。在生物学过程的Gene Ontology分析中，上调的基因显著富集在“细胞外基质组织”、“细胞粘附”和“炎症反应”中，而下调的DEG显著富集在“异生物质代谢过程”、“氧化还原过程”和“类固醇代谢过程”中。在京都基因和基因组百科全书分析中，上调的DEG显著富集在“细胞外基质-受体相互作用”、"粘着斑“和”PI 3 K-Akt信号通路“，而下调的DEG显著富集在”化学致癌“、"细胞色素P450代谢外源性物质”和“过氧化物酶体”。本研究还从DEG中鉴定了10个枢纽基因：肿瘤蛋白p53（TP 53）、C-X-C基序趋化因子配体8（CXCL 8）、四跨膜蛋白4（TSPAN 4）、溶血磷脂酸受体2（LPAR 2）、腺苷酸环化酶3（ADCY 3）、磷酸肌醇-3-激酶调节亚基1（PIK 3R 1）、神经介肽U（NMU）、C-X-C基序趋化因子配体（CXCL 12）、fos原癌基因、AP-1转录因子亚基（FOS）和1-磷酸鞘氨醇受体1（S1 PR 1），与其它DEG的表达水平较高。生存分析显示，ADCY 3、LPAR 2、S1 PR 1、TP 53和TSPAN 4的高表达与较低的生存率相关，而CXCL 8、FOS、NMU和PIK 3R 1的高表达与较高的生存率相关。CXCL 12与生存率之间没有显著相关性。此外，TSPAN 1和TSPAN 8出现在前100名DEG中。最后，观察到与12名患者的癌旁组织相比，4个枢纽基因在胃癌组织中高表达; TSPAN 4的增加是显著的（>5倍）。四跨膜蛋白家族基因可能是胃癌的新的生物标志物。本研究的发现可能会提高对胃癌发生的分子机制的理解。
Gastric cancer has become a serious disease in the past decade. It has the second highest mortality rate among the four most common cancer types, leading to ~700,000 mortalities annually. Previous studies have attempted to elucidate the underlying biological mechanisms of gastric cancer. The present study aimed to obtain useful biomarkers and to improve the understanding of gastric cancer mechanisms at the genetic level. The present study used bioinformatics analysis to identify 1,829 differentially expressed genes (DEGs) which were obtained from the GSE54129 dataset. Using protein-protein interaction information from the Search Tool for the Retrieval of Interacting Genes database, disease modules were constructed for gastric cancer using Cytoscape software. In the Gene Ontology analysis of biology processes, upregulated genes were significantly enriched in ‘extracellular matrix organization’, ‘cell adhesion’ and ‘inflammatory response’, whereas downregulated DEGs were significantly enriched in ‘xenobiotic metabolic process’, ‘oxidation-reduction process’ and ‘steroid metabolic process’. During Kyoto Encyclopedia of Genes and Genomes analysis, upregulated DEGs were significantly enriched in ‘extracellular matrix-receptor interaction’, ‘focal adhesion’ and ‘PI3K-Akt signaling pathway’, whereas the downregulated DEGs were significantly enriched in ‘chemical carcinogenesis’, ‘metabolism of xenobiotics by cytochrome P450’ and ‘peroxisome’. The present study additionally identified 10 hub genes from the DEGs: Tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), tetraspanin 4 (TSPAN4), lysophosphatidic acid receptor 2 (LPAR2), adenylate cyclase 3 (ADCY3), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), neuromedin U (NMU), C-X-C motif chemokine ligand (CXCL12), fos proto-oncogene, AP-1 transcription factor subunit (FOS) and sphingosine-1-phosphate receptor 1 (S1PR1), which have high degrees with other DEGs. The survival analysis revealed that the high expression of ADCY3, LPAR2, S1PR1, TP53 and TSPAN4 was associated with a lower survival rate, whereas high expression of CXCL8, FOS, NMU and PIK3R1 was associated with a higher survival rate. No significant association was identified between CXCL12 and survival rate. Additionally, TSPAN1 and TSPAN8 appeared in the top 100 DEGs. Finally, it was observed that 4 hub genes were highly expressed in gastric cancer tissue compared with para-carcinoma tissue in the 12 patients; the increased TSPAN4 was significant (>5-fold). Tetraspanin family genes may be novel biomarkers of gastric cancer. The findings of the present study may improve the understanding of the molecular mechanisms underlying the development of gastric cancer.
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