丝氨酸—精氨酸蛋白激酶1在乳腺癌中的表达及意义

Expression and Significance of Serine Arginine Protein Kinase 1 in Breast Cancer

目的:探索丝氨酸—精氨酸蛋白激酶1(SRPK1)在乳腺浸润癌中的表达以及与乳腺癌患者临床病理特征的关系,旨在为SRPK1作为乳腺癌的新型标志物提供理论依据。方法:通过UALCAN、TIMER、HPA等数据库分析SRPK1在不同肿瘤中的表达水平、在乳腺浸润癌(BRCA)与正常对照及配对癌旁样本之间的表达差异,同时分析SRPK1与BRCA临床资料的关系。通过TIMER数据库分析在BRCA中SRPK1与浸润免疫细胞的关系。通过STRING数据库,分析与SRPK1高相关蛋白。通过R语言分析TCGA数据库中与SRPK1高相关的基因。结果:SRPK1在多种肿瘤中高表达,BRCA组织中SRPK1的表达水平显著高于正常样本及对应癌旁组织(P<0.001)。在BRCA标本中,SRPK1表达水平与患者疾病分级(stage)、TNM分期和组织学亚型、淋巴结转移、癌症表型、TP53突变等均相关(P<0.05);SRPK1高表达患者总生存率低于低表达患者(P<0.05),SRPK1表达对BRCA诊断曲线下面积(AUC)=0.793(CI:0.757~0.829)。不同种族(race)、性别(gender)、绝经情况(menopausal status)等对SRPK1表达无影响,但(21~40岁)年龄组SRPK1表达高于其他高年龄组(P<0.05)。SRPK1表达在乳腺癌组织中与多种免疫细胞的浸润水平均显著相关(P<0.05)。STRING工具分析SRPK1蛋白的PPI网络,与SRPK1正相关性较高的基因为:BIRC5、AQP9、BCL2A1;负相关性较高的基因为:NAT1、ADH1B。结论:SRPK1在BRCA中高表达并预示不良预后,可作为BRCA的潜在的标志物。

Objective:The expression of serine-arginine protein kinase 1(SRPK1)in breast invasive cancer and its relationship with the clinicopathological characteristics of breast cancer patients to provide a theoretical basis for SRPK1 as a novel marker of breast cancer.Methods:The expression of SRPK1 in different cancers and the expression difference between Breast invasive carcinoma(BRCA)and normal and paired adjacent samples were analyzed by UALCAN,TIMER and HPA,and the relationship between SRPK1 and BRCA was analyzed.The relationship between SRPK1 and infiltrating immune cells in BRCA was analyzed by the TIMER database.Analysis of proteins highly associated with SRPK1 by the STRING database.Genes highly associated with SRPK1 in the TCGA database were analyzed by R language.Results:SRPK1 was highly expressed in various tumors,and the expression level of SRPK1 in BRCA tissues was significantly higher than that of normal samples and corresponding adjacent tissues(P<0.001).In BRCA specimens,SRPK1 expression was correlated with Stage,TNM stage and histological subtype,lymph node metastasis,cancer phenotype,TP53 mutation(P<0.05);the overall survival rate of patients with high SRPK1 expression was lower than low expression(P<0.05),and SRPK1 expression affected the diagnostic area of BRCA(AUC)=0.793(CI:0.757~0.829).Different Races,Gender,Menopausal status had no effect on SRPK1 expression,but(21~40 years)age groups had higher SRPK1 expression than other higher age groups(P<0.05).SRPK1 expression was significantly correlated with the infiltration levels of various immune cells in breast cancer tissues(P<0.05).STRING analyzes the PPI network of SRPK1 protein,the genes with high positive correlation with SRPK1 are BIRC5,AQP9,BCL2A1,and the genes with high negative correlation are NAT1 and ADH1B.Conclusion:SRPK1 is highly expressed in BRCA and predicts a poor prognosis,and can be used as a potential marker of BRCA.