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

Pancreatic cancer (PC) is associated with a poor prognosis. PRKAA1 (AMPK-α1), the catalytic subunit of 5′-adenylate-activated protein kinase (AMPK), plays a crucial role in various stages of tumorigenesis and cancer progression. However, the biological mechanisms of PRKAA1 within the tumor microenvironment remain inadequately explored. In this study, we conducted a comprehensive analysis of data from TCGA and GTEx databases to assess whether PRKAA1 is differentially expressed across a range of tumors. Kaplan-Meier survival curves and Cox regression analyses revealed that the differential expression of PRKAA1 was associated with overall survival across multiple cancers and served as an independent prognostic factor in Brain Lower Grade Glioma (LGG), Acute Myeloid Leukemia (LAML), Liver Hepatocellular Carcinoma (LIHC), Pancreatic Adenocarcinoma (PAAD), and Kidney Chromophobe (KICH). Furthermore, PRKAA1 expression was strongly linked to various immune profiles, suggesting its potential as a target for immunotherapy.

In PC cells, we found that downregulation of PRKAA1 expression led to reduced cell proliferation, migration, and invasion. Additionally, we observed that PRKAA1 likely regulates PC progression via the PI3K/AKT signaling pathway. When cells were treated with AKT inhibitors MK2206 and GSK2110183, the PRKAA1 overexpression group showed reduced sensitivity to these inhibitors compared to the negative control group. Collectively, these findings suggest that PRKAA1 may serve as a valuable prognostic marker and a novel target for tumor immunotherapy.