Hypoxia-induced Long Non-coding RNA LSAMP-AS1 Regulates ceRNA Network to Predict Prognosis for Pancreatic Cancer

Abstract The limited efficacy of chemotherapy and immunotherapy for pancreatic cancer is thought to be largely influenced by the surrounding cancer microenvironment. The hypoxic microenvironment caused by insufficient local blood supply is very important. However, the method to assess the level of hypoxia in the microenvironment of pancreatic cancer (PC) remains unclear. In our research, we downloaded transcriptomic and clinicopathological data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A preliminary risk model was developed to reflect the hypoxic environment of pancreatic cancer. We found that high hypoxia risk score indicated poor long-term survival and the presence of an immunosuppressive microenvironment. In addition, based on prognostic hypoxia-related genes, 177 PC samples were divided into two subtypes using a consistent clustering method. Compared with Cluster2, Cluster1 was defined as the "hypoxic subgroup". The infiltration of CD8 T cells, activated memory CD4 T cells, naive B cells, memory B cells, plasma cells, and neutrophils were lower in cluster1, suggesting that there was significant immunosuppression in cluster 1. Then, we constructed a ceRNA regulatory network composed of differentially expressed lncRNA, miRNA and mRNA. Finally, LSAMP-AS1/hsa-miR-129-5p/S100A2 has been identified as a key ceRNA network that regulates the hypoxic environment and the prognosis of PC.