The current investigation aimed to mine therapeutic molecular targets that play an key part in the advancement of pancreatic ductal adenocarcinoma (PDAC). The expression profiling by high throughput sequencing dataset profile GSE133684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Limma package of R was used to identify differentially expressed genes (DEGs). Functional enrichment analysis of DEGs were performed. Protein-protein interaction (PPI) networks of the DEGs were constructed. An integrated gene regulatory network was built including DEGs, microRNAs (miRNAs), and transcription factors. Furthermore, consistent hub genes were further validated. Molecular docking experiment was conducted. A total of 463 DEGs (232 up regulated and 231 down regulated genes) were identified between very early PDAC and normal control samples. The results of Functional enrichment analysis revealed that the DEGs were significantly enriched in vesicle organization, secretory vesicle, protein dimerization activity, lymphocyte activation, cell surface, transferase activity, transferring phosphorus-containing groups, hemostasis and adaptive immune system. The PPI network and gene regulatory network of up regulated genes and down regulated genes were established, and hub genes were identified. The expression of hub genes (CCNB1, FHL2, HLA-DPA1 and TUBB1) were also validated to be differentially expressed among PDAC and normal control samples. Molecular docking experiment predicted the novel inhibitory molecules for CCNB1 and FHL2. The identification of hub genes in PDAC enhances our understanding of the molecular mechanisms underlying the progression of this disease. These genes may be potential diagnostic biomarkers and/or therapeutic molecular targets in patients with PDAC.

中文翻译：

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结合生物信息学分析和分子对接实验鉴定胰腺导管腺癌分子标记物及其相互作用

当前的研究旨在挖掘在胰腺导管腺癌（PDAC）的发展中起关键作用的治疗性分子靶标。高通量测序数据集概要文件GSE133684数据集的表达谱分析是从基因表达综合（GEO）数据库下载的。R的Limma软件包用于识别差异表达基因（DEG）。进行了DEG的功能富集分析。构造了DEG的蛋白质-蛋白质相互作用（PPI）网络。建立了一个集成的基因调控网络，包括DEG，microRNA（miRNA）和转录因子。此外，进一步验证了一致的毂基因。进行了分子对接实验。在非常早的PDAC和正常对照样品之间共鉴定到463个DEG（232个上调基因和231个下调基因）。功能富集分析的结果表明，DEGs在囊泡组织，分泌囊泡，蛋白二聚活性，淋巴细胞活化，细胞表面，转移酶活性，转移含磷基团，止血和适应性免疫系统中显着富集。建立了上调基因和下调基因的PPI网络和基因调控网络，并鉴定了中枢基因。还验证了毂基因（CCNB1，FHL2，HLA-DPA1和TUBB1）的表达在PDAC和正常对照样品之间是差异表达的。分子对接实验预测了CCNB1和FHL2的新型抑制分子。在PDAC中识别轮毂基因增强了我们对这种疾病进展的分子机制的了解。这些基因可能是PDAC患者的潜在诊断生物标志物和/或治疗分子靶标。