基于公共数据库筛选直肠癌免疫相关的预后基因  

Screening of prognostic genes related to immunity of rectal cancer based on public database

作　　者：葛楠[1] 高飞[1] 杨国旺[1] GE Nan;GAO Fei;YANG Guowang(Department of Oncology,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院肿瘤科,北京100010

出　　处：《国际检验医学杂志》2023年第13期1618-1623,共6页International Journal of Laboratory Medicine

摘　　要：目的通过生物信息学方法分析直肠癌芯片表达数据,筛选出与直肠癌预后相关的潜在基因。方法从基因表达汇编数据库(GEO)中获取直肠癌基因表达数据集GSE87211。使用ESTIMATE算法来计算肿瘤基质评分和免疫评分,评估肿瘤微环境评分与临床特征的相关性,分析高评分组及低评分组的生存差异。筛选两组之间的差异表达基因并进行GO富集分析、KEGG信号通路分析。应用Kaplan-Meier曲线对筛选的基因进行预后分析。利用UALCAN在线网站验证筛选的基因在直肠癌的预后价值。结果高免疫评分/基质评分患者与低免疫评分/基质评分组患者生存预后比较差异无统计学意义(P>0.05)。KRAS基因突变型患者免疫评分低于野生型患者(P<0.05),存在远处转移患者基质评分高于无转移患者(P<0.05)。共得到945个差异共表达基因,其中799个上调基因和146个下调基因。GO分析显示差异共表达基因富集于免疫细胞迁移、趋化、黏附、增殖、活化与调节,细胞膜、细胞外基质、组织相容性复合体Ⅱ等细胞成分,以及受体配体活性、趋化因子活性、细胞因子和受体活性等分子功能。KEGG分析显示,差异共表达基因主要在细胞因子间相互作用、白细胞介素(IL)-17、细胞黏附分子等信号通路富集。通过生存分析及外部数据库验证共筛选出4个基因,分别为ERM样蛋白(ERMN)、受体活性修饰蛋白1(RAMP1)、鞘氨醇1磷酸酯受体3(S1PR3)、肿瘤坏死因子α诱导蛋白2(TNFAIP2),它们在直肠癌患者中的高表达与较差的生存预后有关(P<0.05)。结论ERMN、RAMP1、S1PR3、TNFAIP2高表达可能与直肠癌的不良预后有关,可以为直肠癌的免疫治疗方案的选取提供参考。Objective To screen potential genes related to the prognosis of rectal cancer by analyzing the expression data of rectal cancer microarray using bioinformatics methods.Methods The rectal cancer gene expression dataset GSE87211 was obtained from the Gene Expression Omnibus(GEO)database.The ESTIMATE algorithm was used to calculate the tumor stromal score and immune score,evaluate the correlation between tumor microenvironment score and clinical characteristics,and analyze the survival difference between high score group and low score group.Differentially expressed genes between the two groups were screened,and GO enrichment analysis and KEGG signaling pathway analysis were performed.Kaplan-Meier curve was used to analyze the prognosis of the selected genes.UALCAN online website was used to verify the prognostic value of the screened genes in rectal cancer.Results There was no significant difference in the survival prognosis between patients with high immune score/stromal score and patients with low immune score/stromal score(P>0.05).Patients with KRAS gene mutation had a significantly lower immune score than those with wild type(P<0.05),and patients with distant metastasis had a significantly higher stromal score than those without metastasis(P<0.05).A total of 945 differentially co-expressed genes were obtained,including 799 up-regulated genes and 146 down-regulated genes.GO analysis showed that the differentially co-expressed genes were enriched in immune cell migration,chemotaxis,adhesion,proliferation,activation and regulation,cellular components such as cell membrane,extracellular matrix,major histocompatibility complexⅡ,and molecular functions such as receptor ligand activity,chemokine activity,cytokine and receptor activity.KEGG analysis showed that differentially co-expressed genes were mainly enriched in cytokine interaction,interleukin(IL)-17,cell adhesion molecules and other signaling pathways.Four genes were screened by survival analysis and external database verification,namely ERM-like protein(ERMN)

关 键 词：直肠癌 肿瘤微环境 免疫细胞 基质细胞 预后 

分 类 号：R735.34[医药卫生—肿瘤]