Identification of potential hub genes associated with the pathogenesis and prognosis of pancreatic duct adenocarcinoma using bioinformatics meta‑analysis of multi‑platform datasets

Abstract

Pancreatic duct adenocarcinoma (PDAC) is a highly malignant type of cancer with a low five-year survival rate. Gene alterations are crucial to the molecular pathogenesis of PDAC. Therefore, the present study analyzed gene expression profiles to reveal genes involved in the tumorigenesis of PDAC. A total of eight gene expression profiles (GSE15471, GSE16515, GSE41368, GSE62165, GSE62452, GSE71729, GSE71989 and GSE91035) and a PDAC dataset were acquired from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database, respectively. Differentially expressed genes (DEGs) were screened using functional annotation, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) network construction. A Cox proportional hazards model was then constructed and used to analyze the data. A total of 136 DEGs (67 up- and 69 downregulated genes) were identified between PDAC tissues and normal tissues. The ‘extracellular matrix-related’ genes were the most enriched in the GO term analysis. ‘Pancreatic secretion’, ‘phosphoinositide-3-kinase–protein kinase B/Akt (PI3K-Akt) signaling pathway’, ‘protein digestion and absorption’ and ‘ECM-receptor interaction’ were the most enriched categories in KEGG pathway analysis. Following PPI network construction, the 10 most significant genes [albumin, epidermal growth factor, matrix metalloproteinase (MMP) 9, epidermal growth factor receptor, fibronectin 1, MMP1, plasminogen activator inhibitor-1, tissue inhibitor of metalloproteinase 1, plasminogen activator urokinase (PLAU) and PLAU receptor) exhibiting a high degree of connectivity, were identified as the hub genes likely to be associated with the pathogenesis of PDAC. In addition, a prognostic predictive system for PDAC, composed of five genes (laminin subunit γ 2, laminin subunit β 3, serpin family B member 5, amphiregulin and secreted frizzled related protein 4), was constructed. This was validated in the GSE62452 dataset (using 66 PDAC samples with outcome data) and TCGA PDAC dataset (using 146 PDAC samples with outcome data). In conclusion, the present study revealed potential hub genes involved in PDAC progression, providing directive significance for individualized clinical decision-making and molecular-targeting therapy in patients with PDAC.

PLAU1 Facilitated Proliferation, Invasion, and Metastasis via Interaction With MMP1 in Head and Neck Squamous Carcinoma

“…PLAU1 and MMP1 are associated with the extracellular matrix, cell-cell adhesion, and collagen catabolism in oral squamous carcinoma ( 25 ). PLAU1 and MMP1 play similar roles in malignant tumors and exhibit a high degree of connectivity ( 26 ). Moreover, PLAU1 was shown to promote disease progression through the secretion of matrix metalloproteinases (MMPs) ( 27 ), leading to localized matrix proteolysis ( 28 ).…”

Identification of novel candidate biomarkers and efficacious small molecule drugs for pancreatic adenocarcinoma based on comprehensive bioinformatics technology

“…PAAD is a highly aggressive tumor with dismal prognoses which is resulted by the lack of reliable biomarkers and therapeutic targets [1]. In our exploration, we conducted comprehensive bioinformatics analyses to identify key genes related with the progression of PAAD and finally found three key genes as well as several potential small molecule drugs to treat PAAD.…”

“…Recently, on the basis of big integrated data and bioinformatics, the promising key genes related with cancer development and prognosis can be identified with the widespread popularity of gene chips and the rapid development of high-throughput sequencing technology. Potential hub genes linked with the pathogenesis and outcome of PAAD were screened out using bioinformatics meta-analysis based on the GEO and TCGA databases [1]. Wu et al identified a nine-gene signature and established a prognostic nomogram used to predict the prognoses of PAAD patients [6].…”

From Genetic Alterations to Tumor Microenvironment: The Ariadne’s String in Pancreatic Cancer

“…Moreover, fibronectin-induced EMT correlates with poor OS in surgically resected PC patients [89]. Currently, the use of multi-gene expression profile datasets and meta-analyses has led to the identification of fibronectin as one of ten hubs that may be involved in PC progression and pathogenesis [182]. Along these lines, focal adhesion kinase (FAK) activation downstream of integrin binding to fibronectin and collagens correlates with high levels of fibrosis and poor CD + cytotoxic T cell infiltration in PC; FAK inhibition limited tumor progression, markedly reduced tumor fibrosis, decreased the numbers of tumor-infiltrating immunosuppressive cells, and rendered the previously unresponsive KPC mouse model responsive to T cell immunotherapy and programmed cell death protein (PD)-1 antagonists.…”