Objective: To investigate the copy number variation (CNV) of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in pancreatic cancer and its relationship to the prognosis of pancreatic cancer patients.
Methods: The CNV and RNA Seq V2 data in the Cancer Genome Atlas (TCGA) were used for analysis of correlation between the CDKN2A gene CNV and its mRNA expression, and the influence of CDKN2A gene CNV on the expressions of other genes. The difference in CDKN2A gene expressions between normal subjects and pancreatic cancer patients was compared and the relation of CDKN2A gene CNV with the prognosis of pancreatic cancer patients was analyzed by using TCGA database and GTEx database. Functional enrichment analysis of CDKN2A and its co-expressed genes was performed by using gene ontology analysis (GO analysis) in DIVAD combined with KEGG.
Results: By mining the TCGA database, CDKN2A gene CNV was found to be positively correlated with its mRNA expression (Pearson: r=0.102, Spearman: r=0.257). The expression levels of HOXC6 and SLC2A1 mRNA were significantly increased, while the expression levels of GGA2 and MTAP mRNA were significantly decreased in pancreatic cancer with CDKN2A gene (all P<0.05), and the correlation analysis showed that CDKN2A gene was positively correlated with MTAP mRNA (Pearson: r=0.42, Spearman: r=0.55). The CDKN2A gene expression in pancreatic cancer tissues was found to be significantly higher than that in normal pancreatic tissues by analyzing the GTEx database (P<0.05). The overall survival rate and tumor-free survival rate of pancreatic cancer patients with CDKN2A gene CNV were significantly reduced compared with those without CDKN2A gene CNV (both P<0.05). Functional enrichment analysis of co-expressed genes related to CDKN2A showed that the functions of these co-expressed genes were mainly concentrated in the signal pathways of cell cycle.
Conclusion: CDKN2A gene CNV is an unfavorable prognostic factor for pancreatic cancer and can be used as an indicator for estimating the prognosis of pancreatic cancer.