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Identification of Prognostic Biomarkers by Combined mRNA and miRNA Expression Microarray Analysis in Pancreatic Cancer

机译:联合mRNA和miRNA表达芯片分析对胰腺癌预后生物标志物的鉴定

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摘要

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 (, , , and ) 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.
机译:胰腺癌是癌症相关死亡的第四个主要原因,早期诊断是提高该病存活率的关键之一。分子生物标志物是诊断胰腺癌的重要方法。我们使用来自三个mRNA芯片数据集和一个microRNA数据集(,,和)的数据来识别潜在的关键基因。鉴定出差异表达基因(DEG)和microRNA(DEM)。在所有数据集中对通用DEG进行功能,途径富集和蛋白质-蛋白质相互作用分析。确定了DEM的靶基因。使用整体生存率分析进一步检查也是DEG的DEM目标。总共确定了236个DEG和21个DEM。共有四个DEG(ECT2,NR5A2,NRP2和TGFBI),它们也是DEM的目标基因。总体生存期分析表明,这些基因中的三个(ECT2,NRP2和TGFBI)的高表达水平与胰腺癌患者的总体生存期较差有关。胰腺中DEG的基本表达在各种器官组织中较低。在不同的胰腺癌细胞系中,ECT2和NRP2的表达高于正常胰腺细胞系。 Crispr Cas9基因编辑系统对ECT2的敲除降低了胰腺癌细胞系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中表现良好,而ECT2和NRP2可以作为Crispr Cas9在胰腺癌中的潜在生物标志物或治疗靶标。

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