甲基化驱动基因IFFO1在胰腺癌诊断和预后中的作用及对癌细胞生物学行为的影响  

Exploring the role of methylation-driven gene IFFO1 in pancreatic adenocarcinoma diagnosis,prognosis and cellular functions

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作  者:徐梓淇 胡睿智 李军建 王红霞 桑友洲[4] XU Ziqi;HU Ruizhi;LI Junjian;WANG Hongxia;SANG Youzhou(Department of Oncology,Clinical Medical College,Shanghai General Hospital of Nanjing Medical University,Shanghai 201600,China;School of Life Sciences,Yantai University,Yantai 264006,Shandong Province,China;Department of Oncology Center,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201600,China;Department of Medical Oncology,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China)

机构地区:[1]南京医科大学附属上海一院临床医学院肿瘤科,上海201600 [2]烟台大学生命科学学院,山东烟台264006 [3]上海交通大学医学院附属第一人民医院肿瘤中心,上海201600 [4]复旦大学附属肿瘤医院肿瘤内科,复旦大学上海医学院肿瘤学系,上海200032 [5]复旦大学附属肿瘤医院肿瘤内科

出  处:《中国癌症杂志》2024年第11期998-1010,共13页China Oncology

基  金:国家自然科学基金(82103666);上海市自然科学基金(22ZR1450000)。

摘  要:背景与目的:DNA异常甲基化与肿瘤的发生、发展密切相关。本研究旨在探索胰腺癌(pancreatic adenocarcinoma,PAAD)甲基化驱动基因(methylation-driven gene,MDG)中间丝家族孤儿蛋白1(intermediate filament family orphan 1,IFFO1)在PAAD中的表达、对PAAD细胞侵袭转移的影响,以及作为诊断和预后标志物的潜力。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库、国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库、高通量基因表达(Gene Expression Omnibus,GEO)数据库获取PAAD及其癌旁组织的mRNA表达数据(TCGA-PAAD-mRNA)、DNA甲基化芯片数据(TCGA-PAAD-meth、GSE53051、PACA-AU)以及健康人血液的DNA甲基化芯片数据(GSE69270)。通过差异表达分析联合差异甲基化分析筛选PAAD的MDG。在TCGA数据库中,应用Pearson相关性检验验证IFFO1启动子甲基化水平与其表达水平之间的相关性。同时,通过Kaplan-Meier生存分析评估IFFO1启动子甲基化水平、表达水平与PAAD预后的关系。27例PAAD患者的癌组织及其对应癌旁组织的病理切片来自上海交通大学医学院附属第一人民医院。本研究涉及的所有样本均通过上海交通大学医学院附属第一人民医院人类伦理委员会的审核批准(伦理编号:院伦审[2017]53号)。利用免疫组织化学染色(immunohistochemistry staining,IHC)检测27例PAAD患者的癌组织及其对应癌旁组织中IFFO1的表达。根据IFFO1表达的中位值,将TCGA数据库中的患者分为高表达组和低表达组,并进行差异分析、基因本体论(gene ontology,GO)富集分析及基因集富集分析(gene set enrichment analysis,GSEA)。使用蛋白质印迹法(Western blot)及实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检验正常胰腺导管上皮细胞系H6C7与PAAD细胞系MIA PaCa2、BxPC-3、AsPC-1和Capan-2中IFFO1的表达差异。通过细胞划痕实验和侵袭实验检测过Background and purpose:Abnormal DNA methylation is closely associated with the onset and progression of tumors.This study aimed to investigate the expression of intermediate filament family orphan 1(IFFO1),a methylation-driven gene(MDG)in pancreatic adenocarcinoma(PAAD),along with its effects on the invasion and metastasis of PAAD cells,as well as its potential as a diagnostic and prognostic biomarker.Methods:mRNA expression data(TCGA-PAAD-mRNA),DNA methylation data(TCGA-PAAD-meth,GSE53051,PACA-AU)of PAAD and adjacent normal tissues,as well as DNA methylation data of healthy individuals’blood(GSE69270),were obtained from the The Cancer Genome Atlas(TCGA),International Cancer Genome Consortium(ICGC)and Gene Expression Omnibus(GEO)databases.By performing differential expression analysis combined with differential methylation analysis,we screened for MDG in PAAD.In the TCGA database,Pearson correlation tests were employed to verify the relationship between IFFO1 promoter methylation level and its expression level.Additionally,Kaplan-Meier survival analysis was conducted to evaluate the relationship among IFFO1 promoter methylation level,expression level,and the prognosis of PAAD.Pathological sections of cancer tissues and corresponding adjacent tissues from 27 PAAD patients were obtained from Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine.All samples involved in this study were approved by the human ethics committee of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine(ethics number:hospital ethics review[2017]No.53).Immunohistochemistry staining(IHC)was utilized to detect the expression of IFFO1 in cancer tissues and corresponding adjacent tissues from 27 PAAD patients.Based on the median expression level of IFFO1,patients in the TCGA database were classified into high-expression and low-expression groups.Subsequently,differential analysis,gene ontology(GO)enrichment analysis and gene set enrichment analysis(GSEA)were performed.Western blot and real-time fluores

关 键 词:中间丝家族孤儿蛋白1 胰腺癌 侵袭转移 DNA甲基化 

分 类 号:R735.9[医药卫生—肿瘤]

 

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