首页|食管癌新型生物学标志物的筛选以及外周血mRNA初步验证

食管癌新型生物学标志物的筛选以及外周血mRNA初步验证

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目的 采用生物信息学和实时荧光定量PCR(qRT-PCR)筛选并验证对食管癌(ESCA)发生和发展起关键作用的基因,以期寻找ESCA的新型生物学标志物.方法 检索TCGA数据库,利用韦恩图分析,初步确定ESCA样本中差异表达基因与对无病生存率(DFS)产生最显著影响的基因之间的交叉基因.通过对重叠基因进行蛋白质-蛋白质互作(PPI)网络分析,并进行GO和KEGG功能分析,筛选出与ESCA发生、发展相关的关键潜在基因.利用qRT-PCR对ESCA患者外周血中关键基因mRNA的表达水平进行定量分析并结合患者临床病理参数进行统计学分析,以评估其作为ESCA新型生物学标志物的潜在价值.结果 在TCGA数据库中筛选出的ESCA差异表达基因与无病生存基因交叉后,发现存在明显差异表达的基因 59 个,其中39 个基因上调,20 个基因下调,且上述基因均明显影响患者的DFS.经过PPI网络分析后,确定了15 个核心互作的上调基因,而下调基因没有形成任何互作网络.进一步对这 15 个核心互作基因通过GO和KEGG富集分析,发现纤维连接蛋白 1(FN1)可能是ESCA筛查的潜在生物学标志物.qRT-PCR结果显示,与健康人对照组相比,ESCA患者外周血中FN1 mRNA的表达水平显著升高.结合患者的临床病理参数分析,发现分化程度差、临床病理分期高的ESCA患者外周血FN1 mRNA水平明显升高,且证实FN1 mRNA水平模型能够有效区分食管癌患者和健康人.结论 FN1 mRNA可作为ESCA潜在的非侵入性筛查生物学标志物.
Screening of new biomarkers for esophageal cancer and preliminary verification for peripheral blood mRNA
Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

esophageal cancerfibronectin 1biomarker

薛白、陈平、张玉领、邵启祥、许国莹、郝惠惠、李洪春、蔡伟莉

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徐州医科大学附属医院检验科,江苏徐州 221000

江苏护理职业学院,江苏淮安 223001

淮安市第二人民医院检验科,江苏淮安 223022

食管癌 纤维连接蛋白1 生物学标志物

淮安市自然科学基金研究项目江苏护理职业学院医学领导力计划淮安市自然科学基金研究项目淮安市"天医星"医学检验重点实验室项目

HAB2022392021001HAB202135HAP202004

2024

临床检验杂志
江苏省医学会

临床检验杂志

CSTPCD
影响因子:0.746
ISSN:1001-764X
年,卷(期):2024.42(5)
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