Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.
J Cell Physiol. 2019 Jul;234(7):11023-11036. doi: 10.1002/jcp.27926. Epub 2019 Jan 11.
BACKGROUND: Ovarian cancer is one of the three major malignant tumors of the female reproductive system, and the mortality associated with ovarian cancer ranks first among gynecologic malignant tumors. The pathogenesis of ovarian cancer is not yet clearly defined but elucidating this process would be of great significance for clinical diagnosis, prevention, and treatment. For this study, we used bioinformatics to identify the key pathogenic genes and reveal the potential molecular mechanisms of ovarian cancer; we used immunohistochemistry to validate them. METHODS: We analyzed and integrated four gene expression profiles (GSE14407, GSE18520, GSE26712, and GSE54388), which were downloaded from the Gene Expression Omnibus (GEO) database, with the aim of obtaining a common differentially expressed gene (DEG). Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We then established a protein-protein interaction (PPI) network of the DEGs through the Search Tool for the Retrieval of Interacting Genes (STRING) database and selected hub genes. Finally, survival analysis of the hub genes was performed using a Kmplotter online tool. RESULTS: A total of 226 DEGs were detected after the analysis of the four gene expression profiles; of these, 87 were upregulated genes and 139 were downregulated. GO analysis results showed that DEGs were significantly enriched in biological processes including the G2/M transition of the mitotic cell cycle, the apoptotic process, cell proliferation, blood coagulation, and positive regulation of the canonical Wnt signaling pathway. KEGG analysis results showed that DEGs were particularly enriched in the cell cycle, the p53 signaling pathway, the Wnt signaling pathway, the Ras signaling pathway, the Rap1 signaling pathway, and tyrosine metabolism. We selected 50 hub genes from the PPI network, which had 147 nodes and 655 edges, and 30 of them were associated with the prognosis of ovarian cancer. We performed immunohistochemistry on phosphoserine aminotransferase 1 (PSAT1). PSAT1 was highly expressed in cancer tissues, and its expression level was related to clinical stage and tissue differentiation in ovarian cancer. A Cox proportional risk model suggested that high expression of PSAT1 and late clinical stage were independent risk factors for survival and prognosis of ovarian cancer patients. CONCLUSION: The detection of DEGs using bioinformatics analysis might be crucial to understanding the pathogenesis of ovarian cancer, especially the molecular mechanisms of its development. The association between PSAT1 expression and the occurrence, development, and prognosis of ovarian cancer was further verified by immunohistochemistry. The PSAT1 expression can be used as a prognostic marker to provide a potential target for the diagnosis and treatment of ovarian cancer.
背景:卵巢癌是女性生殖系统三大恶性肿瘤之一,其死亡率在妇科恶性肿瘤中居首位。卵巢癌的发病机制尚不清楚,但阐明这一过程对临床诊断、预防和治疗具有重要意义。本研究采用生物信息学方法鉴定卵巢癌的关键致病基因,揭示其潜在的分子机制,并采用免疫组织化学方法进行验证。
方法:我们分析整合了从基因表达综合数据库(GEO)下载的四个基因表达谱(GSE14407、GSE18520、GSE26712 和 GSE54388),以获得共同的差异表达基因(DEG)。然后,我们使用基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)途径分析数据库(DAVID)进行分析。然后,我们通过搜索基因相互作用(STRING)数据库建立了 DEG 的蛋白质-蛋白质相互作用(PPI)网络,并选择了枢纽基因。最后,我们使用在线 Kmplotter 工具对枢纽基因进行了生存分析。
结果:对四个基因表达谱进行分析后,共检测到 226 个 DEG,其中 87 个上调基因和 139 个下调基因。GO 分析结果表明,DEGs 在包括有丝分裂细胞周期 G2/M 期过渡、细胞凋亡过程、细胞增殖、血液凝固和经典 Wnt 信号通路的正调控等生物学过程中显著富集。KEGG 分析结果表明,DEGs 特别富集于细胞周期、p53 信号通路、Wnt 信号通路、Ras 信号通路、Rap1 信号通路和酪氨酸代谢途径。我们从 PPI 网络中选择了 50 个枢纽基因,该网络有 147 个节点和 655 个边,其中 30 个与卵巢癌的预后相关。我们对磷酸丝氨酸氨基转移酶 1(PSAT1)进行了免疫组织化学检测。PSAT1 在癌组织中高表达,其表达水平与卵巢癌的临床分期和组织分化有关。Cox 比例风险模型表明,PSAT1 高表达和晚期临床分期是卵巢癌患者生存和预后的独立危险因素。
结论:生物信息学分析检测 DEG 可能对理解卵巢癌的发病机制,特别是其发展的分子机制至关重要。免疫组织化学进一步验证了 PSAT1 表达与卵巢癌的发生、发展和预后的关系。PSAT1 的表达可以作为一个预后标志物,为卵巢癌的诊断和治疗提供潜在的靶点。
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