摘要
目的:通过生物信息学的方法分析谷胱甘肽过氧化物酶1(GPX1)在肝癌组织中的表达及意义。方法:从Ualcan数据库获取正常肝组织及原发性肝癌组织GPX1表达数据,在LinkedOmics中检索GPX1的共表达基因,并通过GO富集分析、KEGG通路分析确定这些基因的参与的生物学过程及功能,利用STRING数据库分析相关基因编码蛋白的互作网络。最后利用GEPIA数据库分析GPX1表达与肝癌患者预后的关系。结果:与正常肝组织比较,不同分期(IV期除外)、不同年龄患者肝癌组织中GPX1表达水平均明显升高,且男性肝癌患者肝癌组织中GPX1表达明显高于女性患者(均P<0.05)。GPX1共表达基因主要参与基因转录、翻译、蛋白泛素化、蛋白质磺酰化、mRNA稳定性调节、蛋白酶体复合体、线粒体翻译等分子生物学过程,并参与TGF-β、mTOR、WNT、MAPK、HIF-1α、NF-κB、VEGF、Notch等信号通路及各种癌症疾病通路。10个肝癌相关基因编码的蛋白与GPX1所编码的蛋白存在互作关系。GPX1高表达患者的总生存率、无病生存率均明显低于GPX1低表达患者(P=0.048、P=0.035)。结论:GPX1在肝癌组织中高表达,且与肝癌的发生、发展及预后密切相关,可以作为肝癌筛选、预后预测的标志物之一。
Objective: To analyze the expression of glutathione peroxidase 1(GPX1) in hepatocellular carcinoma(HCC) tissue and its significance by bioinformatics approaches. Methods: The expression data of GPX1 in normal lover tissue and HCC tissue were obtained in Ualcan database, the co-expressed genes of GPX1 were retrieved in LinkedOmics, and the biological processes and functions of these genes were determined by GO enrichment analysis and KEGG pathway analysis. Then, the interaction network of the proteins encoded by the relevant genes was analyzed by using STRING. Finally, the relationship between GPX1 expression and the prognosis of the HCC patients was analyzed based on GEPIA database.Results: Compared with normal liver tissue, the expression levels of GPX1 in HCC tissues from patients with different disease stages(except stage IV) or different ages were significantly increased, further the GPX1 expression levels in HCC tissues from male patients were significantly higher than that from female patients(all P<0.05). The co-expressed genes of GPX1 mainly participated in the biochemical processes such as the transcription and translation of genes, ubiquitination and sulfonylation of proteins, regulation of mRNA stability, and translation of proteasome complex and mitochondria, and were involved in the TGF-β, mTOR, WNT, MAPK, HIF-1α, NF-κB, VEGF and Notch pathways as well as cancer-related pathways. Ten proteins encoded by HCC-related genes were found having interactions with GPX1 encoded protein. The overall survival rates and disease-free survival rates in HCC patients with high GPX1 expression were significantly lower than those in HCC patients with low GPX1 expression(P=0.048, P=0.035).Conclusion: GPX1 expression is increased in HCC tissue, and its expression is closely related to the occurrence and development as well as prognosis of HCC. So, it can be used as a marker for screening and prognosis estimation of HCC.
引文
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