Overexpression of Topoisomerase 2-Alpha Confers a Poor Prognosis in Pancreatic Adenocarcinoma Identified by Co-Expression Analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of human cancer-related death in the developed countries. Its progression and prognosis are influenced by a complex network of gene interactions.

AIMS: The purpose of this study is to explore key genes associated with pancreatic ductal adenocarcinoma and to predict the possible mechanisms.

METHODS: A weighted gene co-expression network was constructed to identify gene modules associated with the progression of PDAC.

RESULTS: In the significant module (R (2) = 0.30), a total of 20 network hub genes were identified, 6 of which were also hub nodes in the protein-protein interaction network of the module genes. In validation, TOP2A has a higher correlation than other hub genes. Also, in the test set (n = 118), TOP2A was more highly expressed in PDAC than normal pancreas samples (P < 0.001). What is more, gene set enrichment analysis demonstrated that eight gene sets (n = 118), "nucleotide excision repair," "P53 signaling pathway," "proteasome," "mismatch repair," "homologous recombination," "DNA replication," "cell cycle," and "base excision repair," were enriched (FDR < 0.05). In gene ontology analysis, TOP2A in the enriched set was associated with cell cycle and cell division. Furthermore, survival analysis indicated that higher expression of TOP2A resulted in the lower overall survival time as well as disease-free survival time.

CONCLUSION: TOP2A was identified in association with the progression and prognosis of PDAC probably by regulating cell cycle and p53 signaling pathway.