胰腺癌诊断和预后关键生物标志物的筛选鉴定和综合分析

柳兴源; 李菁媛; 杨静

doi:10.3971/j.issn.1000-8578.2020.19.0743

胰腺癌诊断和预后关键生物标志物的筛选鉴定和综合分析

Identification and Integrated Analysis of Key Biomarkers for Diagnosis and Prognosis of Pancreatic Adenocarcinoma

摘要

摘要:
目的筛选鉴定胰腺癌进展过程的关键基因和途径, 并进行综合分析。
方法利用GEO2R对胰腺癌基因表达集合GSE15471、GSE16515、GSE28735、GSE62165中差异表达基因(DEGs)进行筛选和识别, 运用DAVID数据库进行GO分析和KEGG通路分析。然后应用STRING数据库构建了蛋白质相互作用(PPI)网络, 并使用Cytoscape和GEPIA对Hub基因进行了鉴定。用反转录定量聚合酶链反应(RT-qPCR)对这些Hub基因的mRNA水平进行定量分析。
结果筛选出181个上调差异表达基因(uDEGs)和64个下调差异表达基因(dDEGs), 分析结果显示uDEGs和dDEGs在细胞成分(CC), 生物过程(BP)和分子功能(MF)中分别富集, 与多条信号通路密切相关。DEGs中degree得分较高的top 25基因。8个基因的差异表达可预测胰腺癌的预后不良。RT-qPCR结果显示这些基因在胰腺癌组织中均有差异表达发生。
结论 MMP14、MMP1、MET、PLAU、ITGA2、KRT19、COL12A1和ITGA3是与胰腺癌进展有关的关键基因。

Abstract:
Objective To screen and identify key genes and pathways involved in the progression of pancreatic adenocarcinoma (PAAD) and to perform an integrated analysis.
Methods GEO2R was commonly used to screen and identify differentially expressed genes (DEGs) in GSE15471, GSE16515, GSE28735 and GSE62165, and the GO and KEGG pathway analyses were performed with DAVID database. Then a proteinprotein interaction (PPI) network was constructed using a STRING database, and Cytoscape and GEPIA were used to identify the Hub genes. Finally, the mRNA levels of these Hub genes were quantitatively analyzed by RT-qPCR.
Results We screened 181 uDEGs and 64 dDEGs, and the analysis results indicated that uDEGs and dDEGs were respectively enriched in cell component (CC), biological process (BP) and molecular functional (MF), and they were closely related to multiple signal pathways. Then, the top 25 genes with high degree score in DEGs were selected. And 8 genes could predict the poor prognosis of PAAD. RT-qPCR showed that these genes were differentially expressed in PAAD tissues.
Conclusion MMP14, MMP1, MET, PLAU, ITGA2, KRT19, COL12A1 and ITGA3 are the key genes associated with the progress of pancreatic cancer.

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