基于加权基因共表达网络分析筛选SCAP基因预测脓毒症发生  

Screening of SCAP genebased on weighted gene co-expression network analysis for predicting sepsis occurrence

作　　者：郝谦 陈勇 HAO Qian;CHEN Yong(Department of Critical Care Medicine,Taikang Tongji(Wuhan)Hospital,Wuhan 430000,Hubei,China)

机构地区：[1]泰康同济(武汉)医院重症医学科,湖北武汉430000

出　　处：《生物医学工程与临床》2022年第2期212-218,共7页Biomedical Engineering and Clinical Medicine

摘　　要：目的拟利用加权基因共表达网络分析(WGCNA)方法筛选出与脓毒症发生、预后相关的关键基因,为今后的研究提供线索。方法从基因表达(GEO)数据库中通过筛选数据集中样本数大于100,含有脓毒症患者和健康对照组,且有脓毒症患者预后情况数据集,筛选到了两个数据集GSE26378和GSE54514(下载时间:2020年12月28日),采用WGCNA方法对GSE54514数据集中163例脓毒症患者和健康对照组基因表达进行分析;筛选出与脓毒症发生和预后相关的核心靶基因并分析其功能。结果GSE54514中男性64例,女性99例;平均年龄55.56岁(标准差17.21岁);GSE26378中平均年龄53.75岁(标准差3.21岁)。利用GSE54514数据集进行WGCNA算法筛选绿松色(TURQUOISE)模块作为核心模块,通过基因本体(GO)和京都基因和基因组百科全书(KEGG)分析提示TURQUOISE模块主要涉及RNA调控表达异常和RNA剪切组成等功能。通过对模块中基因深入分析,筛选出了固醇调节元件结合蛋白裂解激活蛋白(SCAP)可以作为核心靶基因。在内部数据集GSE54514中验证SCAP表达,SCAP在脓毒症患者存活组中表达高于死亡组(9.036±0.032 vs 8.857±0.067)(P<0.01),曲线下面积(AUC)=0.64,P=0.02;在健康对照组表达高于脓毒症组(9.190±0.073 vs 8.990±0.030)(P<0.01),AUC=0.62,P=0.04。在外部数据集GSE26378中,SCAP在脓毒症患者存活组中表达高于死亡组(0.886±0.030 vs 0.730±0.061)(P=0.045),AUC=0.69,P=0.04;在健康对照组表达高于脓毒症组(1.154±0.088 vs 0.863±0.078)(P<0.01),AUC=0.71,P<0.01。GSEA分析提示SCAP在内部和外部数据集中均涉及了T细胞受体及糖代谢功能。结论基于WGCNA筛出的SCAP与脓毒症发生和预后相关,可为脓毒症发生和治疗的研究提供参考依据。Objective To screen occurrence,prognosis related key gene of sepsis by weighted gene co-expression network analysis(WGCNA)method,and provide clues for further research.Methods Two datasets GSE26378 and GSE54514 were screened(download time:December 28 th,2020)from Gene Expression Omnibus(GEO)database by screening the dataset with more than 100 samples,including sepsis patients and healthy control group.The WGCNA method was used to analyze the gene expression of 163 sepsis cases and healthy controls in GSE54514 dataset,and the core target genes associated with sepsis and prognosis were screened.Results A total of 99 females and 64 males in GSE54514 dataset were enrolled,of which mean age was 55.56 years old(standard deviation was 17.21 years old);in GSE26378 dataset,the mean age was 53.75 years old(standard deviation was 3.21 years old);The GSE54514 data set was used to screen TURQUOUSE Module as the core module by WGCNA algorithm.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis demonstrated that TURQUOISE module were associated with RNA degradation and snoRNA processing.Moreover,the srebpcieavage activating protein(SCAP)gene was selected as the core target gene for further analysis in the module.The SCAP expression in internal GSE54514 dataset was verified,and SCAP expression in sepsis survival group was higher than that in death group[9.036±0.032 vs 8.857±0.067;P<0.01;area under curve(AUC)=0.64,P=0.02],and expression in healthy control group was higher than that in sepsis group(9.190±0.073 vs 8.990±0.030;P<0.01;AUC=0.62,P=0.04).In external GSE26378 dataset,SCAP expression in sepsis survival group was higher than that in death group(0.886±0.030 vs0.730±0.061;P=0.045;AUC=0.69,P=0.04),and the expression in healthy control group was higher than that in sepsis group(1.154±0.088 vs 0.863±0.078;P<0.01;AUC=0.71,P<0.01).The GSEA analysis demonstrated that SCAP was associated with T cell receptor signaling pathway and glucose metabolism in both internal and external datasets.Conclusion

关 键 词：脓毒症 GEO数据库 固醇调节元件结合蛋白裂解激活蛋白(SCAP) 加权基因共表达网络分析(WGCNA) 

分 类 号：R631.2[医药卫生—外科学] R392.2[医药卫生—临床医学]