Liu Bin, Yang Hai, Taher Leila, Denz Axel, Grützmann Robert, Pilarsky Christian, Weber Georg F
Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
Division of Bioinformatics, Department of Biology, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Transl Oncol. 2018 Jun;11(3):700-714. doi: 10.1016/j.tranon.2018.03.003. Epub 2018 Apr 6.
Pancreatic cancer is the fourth leading cause for cancer-related death, and early diagnosis is one key to improve the survival rate of this disease. Molecular biomarkers are an important method for diagnostic use in pancreatic cancer. We used data from three mRNA microarray datasets and a microRNA dataset (GSE16515, GSE15471, GSE28735, and GSE41372) to identify potential key genes. Differentially expressed genes (DEGs) and microRNAs (DEMs) were identified. Functional, pathway enrichment, and protein-protein interaction analyses were performed on common DEGs across all datasets. The target genes of the DEMs were identified. DEMs targets that were also DEGs were further scrutinized using overall survival analysis. A total of 236 DEGs and 21 DEMs were identified. There were a total of four DEGs (ECT2, NR5A2, NRP2, and TGFBI), which were also predicted target genes of DEMs. Overall survival analysis showed that high expression levels of three of these genes (ECT2, NRP2, and TGFBI) were associated with poor overall survival for pancreatic cancer patients. The basic expression of DEGs in pancreas stood lower level in various organ tissues. The expression of ECT2 and NRP2 was higher in different pancreatic cancer cell lines than normal pancreas cell line. Knockout of ECT2 by Crispr Cas9 gene editing system decreased proliferation and migration ability in pancreatic cancer cell line MiaPaCa2. In conclusion, we think that data mining method can do well in biomarker screening, and ECT2 and NRP2 can play as potential biomarker or therapy target by Crispr Cas9 in pancreatic cancer.
胰腺癌是癌症相关死亡的第四大主要原因,早期诊断是提高该疾病生存率的关键之一。分子生物标志物是胰腺癌诊断的重要方法。我们使用了来自三个mRNA微阵列数据集和一个microRNA数据集(GSE16515、GSE15471、GSE28735和GSE41372)的数据来识别潜在的关键基因。识别出差异表达基因(DEGs)和microRNA(DEMs)。对所有数据集中的共同DEGs进行功能、通路富集和蛋白质-蛋白质相互作用分析。识别出DEMs的靶基因。使用总生存分析进一步仔细研究也是DEGs的DEMs靶标。总共识别出236个DEGs和21个DEMs。共有四个DEGs(ECT2、NR5A2、NRP2和TGFBI),它们也是DEMs的预测靶基因。总生存分析表明,其中三个基因(ECT2、NRP2和TGFBI)的高表达水平与胰腺癌患者的总生存不良相关。DEGs在胰腺中的基础表达在各种器官组织中处于较低水平。ECT2和NRP2在不同的胰腺癌细胞系中的表达高于正常胰腺细胞系。通过Crispr Cas9基因编辑系统敲除ECT2可降低胰腺癌细胞系MiaPaCa2的增殖和迁移能力。总之,我们认为数据挖掘方法在生物标志物筛选方面表现良好,并且ECT2和NRP2可作为胰腺癌中潜在的生物标志物或治疗靶点,通过Crispr Cas9发挥作用。