Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its etiology remains largely unknown. This study aimed to screen a panel of key genes and to identify their potential impact on the molecular pathways associated with the development of PDAC. Four gene expression profiles, GSE28735, GSE15471, GSE102238, and GSE43795, were downloaded from the Gene Expression Omnibus (GEO) database. The intersection of the differentially expressed genes (DEGs) in each dataset was obtained using Venn analysis. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were subsequently carried out. To screen for hub genes, a protein–protein interaction (PPI) network was constructed. The intersection of the DEGs revealed 7 upregulated and 9 downregulated genes. Upon relaxation of the selection criteria, 58 upregulated and 32 downregulated DEGs were identified. The top 5 biological processes identified by GO analysis involved peptide cross-linking, extracellular matrix (ECM) disassembly, regulation of the fibroblast growth factor receptor signaling pathway, mesoderm morphogenesis, and lipid digestion. The results of KEGG analysis revealed that the DEGs were significantly enriched in pathways involved in protein digestion and absorption, ECM-receptor interaction, pancreatic secretion, and fat digestion and absorption. The top ten hub genes were identified based on the PPI network. In conclusion, the identified hub genes may contribute to the elucidation of the underlying molecular mechanisms of PDAC and serve as promising candidates that can be utilized for the early diagnosis and prognostic prediction of PDAC. However, further experimental validation is required to confirm these results.

Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues

“…Prot2 also associates with FBLN2, known to disrupt the basement membrane to promote metastasis in PDAC by the interaction with MUC4 [48]. Likewise, we identified fibrillar collagen COL3A1, one of the EMT-promoting proteins in PDAC [49], as well as POSTN, a potential myofibroblastic CAF marker found in dense PDAC stroma and particularly linked to ECM-receptor interaction and PI3K/AKT signaling [50], and matricellular protein THBS1, increased during PDAC progression [51]. In line with their stromal content, Prot2 tumors were particularly enriched for both iCAF and myCAF markers (Fig.…”

“…Phosphotyrosine levels were evaluated prior to sample processing by western blotting. Protein samples were denatured in sample running buffer (65% MiliQ, 25% NuPAGE TM LDS Sample Buffer (49), 10% dithiothreitol (DTT) 1 M) and heated 3 min at 95 °C and immediately loaded in 4-12% polyacrylamide gels (Invitrogen TM NuPAGE TM , Thermo Scientific) which were run at 150 V for 90 min. Proteins were then transferred to a nitrocellulose membrane using 100 V for 2 h. To ascertain equal protein loading, Ponceau staining was used at this step.…”

Identifying the Potential Mechanism of Action of SNPs Associated With Breast Cancer Susceptibility With GVITamIN

“…Interestingly, recent studies suggest both a role for FBN1 (Wang et al, 2015 ) and MYOD1 (Cai et al, 2016 ) in breast cancer. Several of the TGs have been also implicated in cancer (Wu et al, 2016 ; Matsubara et al, 2017 ; Li et al, 2019 ).…”

Upregulation of ASPM, BUB1B and SPDL1 in tumor tissues predicts poor survival in patients with pancreatic ductal adenocarcinoma

“…Compared with all other malignancies, PDAC has the poorest prognosis, with a 5% 5-year survival rate and a mean life expectancy of <6 months, which is predominantly due to resistance to standard therapy (20,21). Commonly used tumor markers, such as CA19-9 and CEA, are ineffective for the early detection of PDAC (22).…”