Abstract
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.
Overview
- The study aims to investigate the differential expression of PRKAA1 in various tumors and its role in pancreatic cancer (PC) progression. The methodology used includes a combined analysis of data from TCGA and GTEx databases, Kaplan-Meier curve and Cox regression analyses, and in vitro experiments on PC cells. The primary objective is to determine whether PRKAA1 can be used as a potential prognostic marker and new target for tumor immunotherapy in PC.
Comparative Analysis & Findings
- The study found that the differential expression of PRKAA1 affected overall survival in a variety of tumors, including 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. In vitro experiments on PC cells revealed that the downregulation of PRKAA1 expression reduced the proliferation, migration, and invasion of PC cells. 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.
Implications and Future Directions
- The study's findings suggest that PRKAA1 can be used as a potential prognostic marker and new target for tumor immunotherapy in PC. Future research directions could include further investigation of the immune profiles associated with PRKAA1 and the development of targeted immunotherapies based on these profiles. In addition, the study highlights the importance of the PI3K/AKT signaling pathway in PC progression and suggests that targeting this pathway could be a promising therapeutic approach.