Abstract
BACKGROUND: Hypoxia plays a significant role in the pathogenesis of pancreatic cancer, but the effect of hypoxia-related genes in pancreatic cancer remains to be elucidated. This study aimed to identify hypoxia-related genes related to pancreatic cancer and construct a prognostic signature. METHODS: Pancreatic cancer datasets were retrieved from TCGA database. Cox regression analyses were used to identify hypoxia-related genes and construct a prognostic signature. Datasets from International Cancer Genome Consortium and GEO databases were used as validated cohorts. The CIBERSORT method was applied to estimate the fractions of immune cell types. DNA methylation and protein levels of the genes in pancreatic cancer were examined. RESULTS: Three hypoxia-related genes (TES, LDHA, and ANXA2) were identified as associated with patient survival and selected to construct a prognostic signature. Patients were divided into high- and low-risk groups based on the signature. Those in the high-risk group showed worse survival than those in the low-risk group. The signature was shown to be involved in the HIF-1 signaling pathway. The time-dependent ROC analyses of three independent validated cohorts further revealed that this signature had a better prognostic value in the prediction of the survival of pancreatic cancer patients. Immune cells analysis for three datasets demonstrated that high-risk signature was significantly associated with macrophages and T cells. DNA methylation and protein levels of the three genes validated their aberrant expression in pancreatic cancer. CONCLUSIONS: Our research provided a novel and reliable prognostic signature that composes of three hypoxia-related genes to estimate the prognosis of pancreatic cancer.