特异性蛋白1在原发性肝癌中的表达及临床意义

Expression and clinical significance of specificity protein 1 in primary liver cancer

目的:探究特异性蛋白1(SP1)在肝癌组织中的表达及其与相关临床特征的关联,分析其在肝癌中的诊断和预后价值。方法:选取华中科技大学同济医学院附属武汉中心医院2017年1月至2019年1月期间30例住院接受手术切除的肝细胞肝癌患者的癌和对应癌旁组织标本,其中男28例、女2例,年龄(48.0±7.3)岁。采用免疫组织化学方法(IHC)检测SP1的表达。从高通量基因表达数据库(GEO)和癌症基因组图谱(TCGA)数据库中下载肝癌患者的基因表达数据以及临床信息,以分析SP1在癌和癌旁组织中的差异表达。利用受试者工作特征曲线(ROC)评估SP1区分肝癌和正常组织的能力。根据SP1表达中位数,将患者分为高表达组(181例)和低表达组(181例),并进行Kaplan-Meier生存分析。利用基因集富集分析(GSEA)研究SP1调控的潜在分子机制。结果:IHC显示SP1在肝癌组织中的阳性表达率明显高于癌旁组织[80%(24/30)比40%(12/30),χ^(2)=8.403,P<0.01]。对TCGA和GEO数据集分析显示SP1的表达水平与肝癌分化程度相关(r=0.197,P<0.01);ROC分析表明,SP1诊断肝癌的ROC曲线下面积均大于0.7;Kaplan-Meier分析显示高表达SP1肝癌患者的总体生存期(OS)低于低表达SP1的肝癌患者(中位OS:3.83年比4.91年,χ^(2)=4.592,P<0.05);单因素COX回归分析显示SP1是影响肝癌预后的危险因素(风险比=1.463,95%可信区间:1.031~2.077,P<0.05);GSEA分析显示,高表达SP1肝癌中Wnt、细胞周期等细胞通路显著富集。结论:SP1在肝癌中高表达。

Objective This study aimed to investigate the expression of specificity protein 1(SP1)and its association with clinical features,and to analyze its diagnostic and prognostic value in HCC.Methods Cancer and corresponding paracancerous tissue specimens of 30 HCC patients who underwent surgical resection at Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,between January 2017 and January 2019.with 28 males and 2 females,and an average age of(48.0±7.3)years.Immunohistochemistry(IHC)was employed to assess SP1 expression.Meanwhile,gene expression datasets and clinical information were obtained from the Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases to analyze SP1 level in HCC.The receiver operating characteristic(ROC)curve was applied to assess the efficacy of SP1 in diagnosing HCC.HCC patients were categorized into high-expression(n=181)and low-expression(n=181)groups based on the median SP1 level and Kaplan-Meier survival analysis was performed.Gene set enrichment analysis(GSEA)was utilized to investigate potential signaling pathways regulated by SP1.Results IHC showed that the positive expression rate of SP1 was significantly higher in HCC than in paracancerous tissue[80%(24/30)vs.40%(12/30),χ^(2)=8.403,P<0.01].Analysis of TCGA and GEO datasets showed that SP1 levels correlated with the degree of HCC differentiation(r=0.197,P<0.01).The ROC analysis indicated that the area under the curve for the diagnosis of HCC by SP1 was greater than 0.7 in all datasets;Kaplan-Meier analysis showed lower overall survival(OS)of HCC patients with high SP1 expression than those with low SP1 expression(median OS:3.83 years vs.4.91 years,χ^(2)=4.592,P<0.05).Univariate COX regression analysis showed that SP1 was a risk factor affecting the prognosis of HCC[hazard ratio(HR)=1.463,95%confidence interval(CI):(1.031-2.077),P<0.05].GSEA analysis revealed cellular pathways such as Wnt and cell cycle were significantly enriched in the high SP1 expression group.Conclusion SP1 is highly expressed and associated with poor prognosis of HCC patients.SP1 may serve as a molecular marker for diagnosing HCC.