AMP‑activated protein kinase family member 5 is an independent prognostic indicator of pancreatic adenocarcinoma: A study based on The Cancer Genome Atlas.

Abstract

Pancreatic adenocarcinoma (PAAD) is a common and highly malignant tumor. The identification of prognostic biomarkers for PAAD could provide invaluable information for clinical treatment. AMP-activated protein kinase family member 5 (ARK5) is a member of the AMPK family that mediates the migration of PAAD cells. In the present study, ARK5 expression was evaluated using bioinformatics analysis in public datasets from The Cancer Genome Atlas. The expression levels of ARK5 in PAAD tumor tissue were significantly increased, compared with matched non-cancerous tissues. ARK5 target genes were then predicted and Gene Ontology Biological Processes, Kyoto Encyclopedia of Genes and Genomes pathway analysis and Reactome gene sets were used to determine the functions associated with the target genes. A protein-protein interaction network was also constructed to find out the node genes and observe their association with the overall survival rate of PAAD. A total of nine node genes were identified in the PPI network, of which six were significantly upregulated in PAAD tissue, compared with matched normal tissue. The prognostic value of each node gene was evaluated by comparing the overall survival in patients with PAAD stratified according to the expression levels of these genes. Overall survival was significantly reduced in patients with high polo-like kinase-1 (PLK1) or protein phosphatase 1 catalytic subunit β (PPP1CB) expression, compared with patients with low expression of these genes. To further evaluate the relationship between PAAD and ARK5, ARK5 immunohistochemical staining was performed in a tissue microarray consisting of 112 tumor samples from patients with PAAD and adjacent normal tissue samples. ARK5 protein expression in PAAD tissue was markedly increased, compared with non-cancerous tissue (P=7.631×10−11). Moreover, ARK5 protein levels were associated with N stage (P=0.018). The overall survival of patients with PAAD with high ARK5 protein expression levels was reduced (P=0.014), compared with patients with low expression. In conclusion, these findings suggested that ARK5 may represent an independent prognostic indicator of PAAD.