Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Integrated Bioinformatics Analysis and Molecular Docking Experiments

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.