FOXO1在甲状腺乳头状癌组织中的表达及其临床意义  

Expression and clinical significance of FOXO1 in thyroid papillary carcinoma tissue

作　　者：韦干观 李柳艳 危丹明[2] 庞玉艳[2] 陈罡[2] 史琳 WEI Gan-guan;LI Liu-yan;WEI Dan-ming;PANG Yu-yan;CHEN Gang;SHI Lin(Department of Otorhinolaryngology Head and Neck Surgery,Guilin People’s Hospital,Guilin 541002,Guangxi,China;Department of Pathology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China;Department of Pathology,The Second Affiliated Hospital of Guangxi Medical University,Nanning 530007,Guangxi,China)

机构地区：[1]桂林市人民医院耳鼻咽喉头颈外科,广西桂林541002 [2]广西医科大学第一附属医院病理科,广西南宁530021 [3]广西医科大学第二附属医院病理科,广西南宁530007

出　　处：《生物医学工程与临床》2025年第2期240-249,共10页Biomedical Engineering and Clinical Medicine

基　　金：广西壮族自治区卫生健康委员会科研课题(Z20191026,Z20201138);广西医科大学第二附属医院优秀后备人才项目(HBRC201804)。

摘　　要：目的检测叉头框蛋白O1(FOXO1)在甲状腺乳头状癌(PTC)患者中的表达,探讨其潜在的分子机制。方法收集90例PTC及23例非癌甲状腺组织(组织芯片编号THC1021和THC961,桂林泛谱公司),以及40例PTC和64例非癌甲状腺组织样本(广西医科大学第一附属医院提供)。通过免疫组化检测FOXO1在PTC中的表达情况,利用基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和ArrayExpress多个高通量人群数据库进行FOXO1 mRNA表达同步验证。采用单细胞测序数据评估FOXO1在PTC细胞中的表达。此外,实验探索了FOXO1可能发挥生物学功能的方式,整合FOXO1的相关基因、FOXO1的靶基因与PTC上调的差异表达基因(UDEG),取交集并进行基因本体(GO)富集、京都基因与基因组百科全书(KEGG)通路和蛋白-蛋白相互作用(PPI)分析。结果免疫组化显示PTC(n=130)中FOXO1表达显著低于非癌甲状腺组织(n=87)。高通量人群数据库分析结果发现,在11个高通量平台中,7个数据集显示PTC中FOXO1 mRNA表达水平较非癌组织下调(P<0.05),标准平均差(SMD)为-0.29(95%CI=-0.38~-0.20),低表达FOXO1的汇总受试者工作特性(sROC)的曲线下面积(AUC)为0.70(95%CI=0.66~0.74)。单细胞测序分析结果显示,FOXO1表达水平也在PTC细胞中显著下调(P<0.0001)。在GO注释中,生物过程(BP)、细胞成分(CC)和分子功能(MF)的排名靠前的项分别是细胞外基质组织、细胞外基质、细胞因子活性。KEGG的主要通路是癌症通路及PI3K-AKt信号通路。结论实验发现FOXO1的下调可能在PTC的发生、发展中起重要作用。Objective To detect the expression of forkhead box O1(FOXO1)in patients with papillary thyroid carcinoma(PTC),and explore its potential molecular mechanism.Methods A total of 90 cases of PTC and 23 of non-cancerous thyroid tissues(tissue chip number THC1021 and THC961,Guilin Fanpu Company),as well as 40 cases of PTC and 64 of non-cancerous thyroid tissue samples(provided by the First Affiliated Hospital of Guangxi Medical University)were collected.The expression of FOXO1 in PTC was detected by immunohistochemistry,and the expression of FOXO1 mRNA was verified by gene expression comprehensive database(GEO),cancer genome atlas(TCGA)and ArrayExpress high-throughput population database.The expression of FOXO1 in PTC cells was evaluated by single cell sequencing data.In addition,the possible biological functions of FOXO1 were explored.The related genes of FOXO1,target genes of FOXO1 and up-regulated differentially expressed genes(UDEG)of PTC were integrated,and gene ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and protein-protein interaction(PPI)analysis were performed.Results The immunohistochemistry showed that FOXO1 expression in PTC(n=130)was significantly lower than that in non-cancerous thyroid tissues(n=87).The results of high-throughput population database analysis showed that the expression level of FOXO1 mRNA in PTC was lower than that in non-cancerous tissues in 7 datasets of 11 high-throughput platforms(P<0.05).The standard mean difference(SMD)was-0.29(95%CI=-0.38--0.20).The area under curve(AUC)of the summary receiver operating characteristic(sROC)of low expression of FOXO1 was 0.70(95%CI=0.66-0.74).Moreover,single-cell sequencing analysis showed that the expression level of FOXO1 was also significantly down-regulated in PTC cells(P<0.0001).In GO annotation,top-ranked categories for biological processes(BP),cellular components(CC),and molecular functions(MF)included extracellular matrix organization,extracellular matrix,and cytokine activity,respectively.The main KEGG pathwa

关 键 词：FOXO1 甲状腺乳头状癌 免疫组化 RNA-SEQ 基因芯片 scRNA-seq 

分 类 号：R736.1[医药卫生—肿瘤] Q75[医药卫生—临床医学]