Therefore, single-cell analysis is needed to explore the functional roles of PRKAA2 in the TME. Dynamic interactions between these cells are a major determinant of tumor pathophysiology. Stromal cells, which are the most active cell type in the tumor microenvironment (TME), predominantly consist of endothelial cells, epithelial cells, fibroblasts, and immune cells, including T cells, B cells, neutrophils, and macrophages. The resulting risk scores were closely linked to immunotherapy responses in patients with head and neck squamous cell carcinoma. constructed a risk model using PRKAA2 and eight other genes.
PRKAA2 may influence tumor immunity in some cancer types. Thus, PRKAA2 is a potential target for new therapeutic strategies. Changes in PRKAA2 expression have been linked to the occurrence, development, and prognosis of multiple tumor types, including breast cancer, ovarian cancer, gastric cancer, kidney cancer, and liver hepatocellular carcinoma. PRKAA2 plays important roles in both tumor initiation and progression, including the regulation of mTOR kinase activity and the maintenance of NADPH levels. However, the tissue and substrate specificity of AMPK complexes are unclear.ĪMPKα2 is encoded by the PRKAA2 gene. In addition, many AMPK substrates are distributed in cells and tissues. AMPK subunits are distributed differently in tissues and organs, and the distribution may be related to the regulation of tissue-specific target molecules. The expression of heterotrimeric complexes of AMPK varies widely in mammalian eukaryotic cells. Theoretically, human AMPK can form 12 different isoforms, depending on the combination of subunit subtypes. AMPK activates or inhibits metabolic-related pathways in response to changes in intracellular AMP/ATP ratios. Therefore, new effective diagnostic, prognostic, and therapeutic biomarkers based on single-cell analyses are urgently needed to develop personalized therapeutic strategies against LIHC.Īdenosine monophosphate-activated kinase (AMPK), a serine/threonine protein kinase, consists of AMPKα (catalytic core α1 or α2), AMPKβ and AMPKγ (regulatory units β1 or β2, and γ1, γ2, or γ3). LIHC is an extremely heterogeneous tumor, which limits the efficacy of cancer therapies. Although these drugs have achieved significant success in the treatment of LIHC, treatment benefits are limited to a small subset of patients. The current drugs for treating LIHC include sorafenib, lenvatinib, and regorafenib, which are multitarget tyrosine kinase inhibitors, and atezolizumab, pembrolizumab, nivolumab, and ipilimumab, which are immunotherapeutic agents. Thus, the prognosis for patients with LIHC is very poor. LIHC is highly aggressive and therapeutic options are limited. Liver hepatocellular carcinoma (LIHC) is the main histological subtype of primary liver cancer. Our study indicate that PRKAA2 may contribute to LIHC progression by promoting metabolic reprogramming and tumor immune escape through theoretical analysis, which offers a theoretical foundation for developing PRKAA2-based strategies for personalized LIHC treatment. This result is supported by the following evidence: 1) the inhibition of major histocompatibility complex class I (MHC-I) expression through the regulation of interferon-gamma activity in malignant cells 2) the promotion of CD8+ T-cell exhaustion and the formation of CD4+ Treg cells in T cells 3) altered interactions between malignant cells and T cells in the tumor immune environment and 4) induction of metabolic reprogramming in malignant cells. High PRKAA2 expression significantly promoted LIHC immune escape. Tumors with high PRKAA2 expression displayed an immune cold phenotype. PRKAA2 was highly expressed in LIHC tissues and was associated with poor patient prognosis. ResultsĪMPK subunits were expressed in tissue-specific and substrate-specific patterns. Functional experiments were performed in LIHC HepG2 cells. In addition, the association between PRKAA2 expression and T-cell evolution during tumor progression was explored using Pseudotime analysis, and the role of PRKAA2 in metabolic reprogramming was explored using the R “ scMetabolis” package. Using the single-cell RNA-sequencing dataset for LIHC obtained from the China National Genebank Database, the communication between malignant cells and T cells in response to different PRKAA2 expression patterns was evaluated. RNA-seq data were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression databases.
However, the role of AMPKα2 in the LIHC tumor immune environment is unclear. AMPKα2, an α2 subunit of AMPK, is encoded by PRKAA2, and functions as the catalytic core of AMPK.
Adenosine monophosphate-activated protein kinase (AMPK) is associated with the development of liver hepatocellular carcinoma (LIHC).