Zhou Jun, Hui Xiaoliang, Mao Ying, Fan Liya
Department of General Ward 1, Zhejiang Hospital of Lingyin District, Zhejiang, China.
Department of Gastroenterology, Zhejiang Hospital of Sandun District, Zhejiang, China
Biosci Rep. 2019 Aug 2;39(8). doi: 10.1042/BSR20190625. Print 2019 Aug 30.
Pancreatic ductal adenocarcinoma (PDAC) is a class of the commonest malignant carcinomas. The present study aimed to elucidate the potential biomarker and prognostic targets in PDAC. The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) in PDAC were obtained by using GEO2R, and overlapped DEGs were acquired with Venn Diagrams. Functional enrichment analysis of overlapped DEGs and DEmiRNAs was conducted with Metascape and FunRich, respectively. The protein-protein interaction (PPI) network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) of DEmiRNAs and hub genes were investigated by Kaplan-Meier (KM) plotter (KM plotter). Transcriptional data and correlation analyses among hub genes were verified through GEPIA and Human Protein Atlas (HPA). Additionally, miRNA targets were searched using miRTarBase, then miRNA-DEG regulatory network was visualized with Cytoscape. A total of 32 DEmiRNAs and 150 overlapped DEGs were identified, and Metascape showed that DEGs were significantly enriched in cellular chemical homeostasis and pathways in cancer, while DEmiRNAs were mainly enriched in signal transduction and Glypican pathway. Moreover, seven hub genes with a high degree, namely, V-myc avian myelocytomatosis viral oncogene homolog (MYC), solute carrier family 2 member 1 (SLC2A1), PKM, plasminogen activator, urokinase (PLAU), peroxisome proliferator activated receptor γ (PPARG), MET proto-oncogene, receptor tyrosine kinase (MET), and integrin subunit α 3 (ITGA3), were identified and found to be up-regulated between PDAC and normal tissues. miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.
胰腺导管腺癌（PDAC）是一类最常见的恶性肿瘤。本研究旨在阐明PDAC中的潜在生物标志物和预后靶点。从基因表达综合数据库（GEO）下载了GSE41368、GSE43795、GSE55643和GSE41369的阵列数据。使用GEO2R获得PDAC中的差异表达基因（DEGs）和差异表达微小RNA（DEmiRNAs），并通过维恩图获得重叠的DEGs。分别使用Metascape和FunRich对重叠的DEGs和DEmiRNAs进行功能富集分析。通过STRING构建重叠DEGs的蛋白质-蛋白质相互作用（PPI）网络，并用Cytoscape进行可视化。通过Kaplan-Meier（KM）绘图仪（KM plotter）研究DEmiRNAs和枢纽基因的总生存期（OS）。通过GEPIA和人类蛋白质图谱（HPA）验证枢纽基因之间的转录数据和相关性分析。此外，使用miRTarBase搜索miRNA靶点，然后用Cytoscape可视化miRNA-DEG调控网络。共鉴定出32个DEmiRNAs和150个重叠的DEGs，Metascape显示DEGs在细胞化学稳态和癌症通路中显著富集，而DEmiRNAs主要富集在信号转导和磷脂酰肌醇蛋白聚糖途径中。此外，鉴定出7个高度连接的枢纽基因，即V-myc禽骨髓细胞瘤病毒癌基因同源物（MYC）、溶质载体家族2成员1（SLC2A1）、丙酮酸激酶M2（PKM）、尿激酶型纤溶酶原激活剂（PLAU）、过氧化物酶体增殖物激活受体γ（PPARG）、原癌基因MET、受体酪氨酸激酶（MET）和整合素亚基α3（ITGA3），发现它们在PDAC和正常组织之间上调。miR-135b、miR-221、miR-21、miR-27a、miR-199b-5p、miR-143、miR-196a、miR-655、miR-455-3p、miR-744和枢纽基因预测PDAC的OS较差。综合生物信息学分析鉴定出几个枢纽基因，它们可能作为PDAC早期诊断和精准靶向治疗的潜在生物标志物或靶点。
