AMP-dependent protein kinase alpha 1 predicts cancer prognosis and immunotherapy response: from pan-cancer analysis to experimental validation

Pancreatic cancer (PC) has poor prognosis. PRKAA1 (AMPK-α1) is the catalytic subunit of 5'-adenylate-activated protein kinase (AMPK), which plays a critical role in multiple stages of tumorigenesis and development. However, the biological mechanisms of PRKAA1 in the tumor microenvironment have not been well studied. In this study, we performed a combined analysis of data from TCGA and GTEx databases to determine whether PRKAA1 is differentially expressed in a variety of tumors. Kaplan-Meier curve and Cox regression analyses indicated that the differential expression of PRKAA1 affected overall survival in a variety of tumors and was an independent prognostic factor for Brain Lower Grade Glioma (LGG), Brain Lower Grade Glioma (LAML), Liver hepatocellular carcinoma (LIHC), Pancreatic adenocarcinoma (PAAD), and Pancreatic adenocarcinoma (KICH). PRKAA1 was closely associated with various immune profiles, suggesting that PRKAA1 can be used for direct immunotherapy. We investigated the role of PRKAA1 in PC cells. We found that the downregulation of PRKAA1 expression reduced the proliferation, migration, and invasion of PC cells. In addition, we found that PRKAA1 regulated PC progression, possibly through the PI3K/AKT signaling pathway. Treatment of cells with the AKT inhibitors MK2206 and GSK2110183 revealed that the PRKAA1 overexpression group was less sensitive to AKT inhibitors than the negative control group. Taken together, PRKAA1 can be used as a potential prognostic marker and new target for tumor immunotherapy.