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基于生物信息学研究性别决定区Y框4在肝细胞癌中的表达及临床意义
汪宇,谢燕婷,王毅州,夏勇*
0
(海军军医大学(第二军医大学)东方肝胆外科医院肝外四科, 上海 200438
*通信作者)
摘要:
目的 研究性别决定区Y框4(SOX4)在肝细胞癌组织中的表达及其与肝细胞癌临床病理特征和预后的关系。方法 采用生物信息学方法分析、挖掘肿瘤基因公共数据库,研究SOX4基因在肝细胞癌中的差异表达,分析SOX4基因表达与肝细胞癌临床病理特征的关系;采用Kaplan-Meier法分析SOX4基因表达与肝细胞癌患者预后的关系;通过基因集富集分析(GSEA)探索肝细胞癌中SOX4基因相关的生物学过程和信号通路。结果 SOX4 mRNA在肝细胞癌组织中的表达水平高于癌旁组织(P<0.01),且与肝细胞癌的肿瘤分期和肿瘤大小有关(P<0.01,P<0.05)。SOX4低表达组肝细胞癌患者的总生存期和无复发生存期均长于SOX4高表达组患者(P均<0.01),且在不同的肝细胞癌分期亚组中均呈现相同的预后趋势。多因素Cox回归分析结果表明SOX4基因表达水平是肝细胞癌患者的独立预后因素(P<0.01)。SOX4基因主要通过调控DNA复制、肌醇需求酶1介导的未折叠蛋白反应、有丝分裂细胞周期阻滞、肿瘤蛋白p53活性和Wnt信号通路等在肝细胞癌中发挥致癌基因作用。结论 SOX4基因在肝细胞癌组织中表达增加,与肝细胞癌患者的不良预后有关。
关键词:  肝细胞癌  性别决定区Y框4  生物信息学  预后
DOI:10.16781/j.0258-879x.2021.09.0975
投稿时间:2021-03-25修订日期:2021-06-07
基金项目:上海市卫生健康委员会课题(2018BR34).
Expression and clinical significance of sex-determining region Y-box 4 in hepatocellular carcinoma based on bioinformatics
WANG Yu,XIE Yan-ting,WANG Yi-zhou,XIA Yong*
(Department of Hepatic Surgery (Ⅳ), Eastern Hepatobiliary Surgery Hospital, Naval Medical University (Second Military Medical University), Shanghai 200438, China
*Corresponding author)
Abstract:
Objective To study the expression of sex-determining region Y-box 4 (SOX4) in hepatocellular carcinoma (HCC) and its relationship with clinicopathological features and prognosis of HCC. Methods The differential expression of SOX4 in HCC was studied through analying and mining the public database of tumor genes by bioinformatics method, and the relationship between SOX4 expression and clinicopathological characteristics was analyzed; the relationship between SOX4 expression and prognosis of HCC patients was analyzed by Kaplan-Meier method; and SOX4-related biological processes and signal pathways in HCC were explored by Gene Set Enrichment Analysis (GSEA). Results The expression level of SOX4 mRNA in HCC tissues was significantly higher than that in the adjacent tissues (P<0.01), and was significantly correlated with tumor stage and tumor size (P<0.01, P<0.05). The overall survival and recurrence-free survival of HCC patients in SOX4 low-expression group were longer than those of patients in SOX4 high-expression group (both P<0.01), and showed the same prognostic trend in different stages of HCC. Multivariate Cox regression analysis showed that the expression level of SOX4 was an independent prognostic factor of HCC patients (P<0.01). SOX4 played an oncogenic role in HCC by regulating DNA replication, inositol-requiring enzyme 1 (IRE1)-mediated unfolded protein response, mitotic cell cycle arrest, tumor protein p53 activity, Wnt signaling pathways and so on. Conclusion The expression of SOX4 is increased in HCC tissues, and is related to poor prognosis.
Key words:  hepatocellular carcinoma  sex-determining region Y-box 4  bioinformatics  prognosis