Bioinformatics analysis of hypoxic markers in cervical cancer via big data
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摘要: 目的 在GEO(gene expression omnibus)和TCGA(the cancer genome atlas)数据库中挖掘宫颈癌缺氧标志物并对其预后进行生存分析。方法 利用GEO数据库中宫颈癌表达谱(GSE75034)缺氧组织和非缺氧组织中的数据进行差异性分析,再运用基因功能分析(gene ontology,GO)与通路富集分析(kyoto encyclopedia of genes and genomes,KEGG)筛选出相关的通路和相关功能的基因,结合TCGA数据库中宫颈癌的数据对其预后运用Kaplan-Meier与Log-rank检验方法进行生存分析。结果 显示有337个基因表达存在差异,缺氧组织中上调的基因有184个,下调的有153个。GO分析显示这些基因与免疫反应、炎症反应、细胞增殖、血管形成等有关;KEGG分析显示主要富集在TNF信号通路、PI3K-Akt信号通路、HIF-1信号通路等。生存分析显示富集在HIF-1通路上的PAI-1、BCL-2、HK-2与宫颈癌病人预后相关,其中PAI-1、HK-2是预后的危险因素(均有P<0.05),高表达组与患者生存期缩短相关,BCL-2是保护因素(χ2=6.508,P=0.011),高表达组与患者生存期延长相关。结论 PAI-1、BCL-2、HK-2可以作为宫颈癌缺氧生物标志物,与宫颈癌病人的预后相关,为后续的研究提供新思路。Abstract: Objective To investigate the hypoxic markers in cervical cancer and its prognostic value via GEO (gene expression omnibus) and TCGA (the cancer genome atlas) database. Methods The datasets of cervical cancer were downloaded from GEO and TCGA database. Hypoxic markers in cervical cancer were explored via GSE75034 database.Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze gene functions. Kaplan-Meier and log-rank test were used to study the prognostic value via TCGA database. Results A total of 337 genes had different expression levels between hypoxic tissues and non-hypoxic tissues, of which 184 genes were upregulated and 153 genes were downregulated. GO analysis showed these genes were related to immune response, inflammation, cell proliferation, angiogenesis, etc. KEGG analysis showed that these genes were enriched in TNF signaling pathway, PI3K-Akt signaling pathway and HIF-1 signaling pathway. Moreover, TCGA data analysis showed PAI-1, BCL-2, HK-2 which enriched in HIF-1 signaling pathway were related to cervical cancer patient prognosis. High levels of PAI-1 and HK-2 expression were significantly correlated with shortened survival (all P<0.05), which indicated a worse outcome, whereas high level of BCL-2 expression was significantly correlated with a prolonged survival (χ2=6.508,P=0.011), suggesting BCL-2 was a protective factor. Conclusions Our results suggested that PAI-1, BCL-2 and HK-2 could be promising hypoxia biomarkers for the prognosis of cervical cancer.
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Key words:
- Uterine cervical neoplasms /
- Anoxia /
- Database
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