Prognosis and Immunological Characteristics of PGK1 in Lung Adenocarcinoma: A Systematic Analysis

Abstract

Aerobic glycolysis plays a key role in tumor metabolic reprogramming to reshape the immune microenvironment. The phosphoglycerate kinase 1 (PGK1) gene codes a glycolytic enzyme that converts 1,3-diphosphoglycerate to 3-phosphoglycerate. However, in lung adenocarcinoma (LUAD), the role of PGK1 in altering the tumor microenvironment (TME) has not yet been determined. Methods: Raw data, including bulk DNA and mRNA-seq data, methylation modification data, single-cell RNA-seq data, proteomics data, clinical case characteristics survival, immunotherapy data, and so on, were obtained from multiple independent public data sets. These data were reanalyzed to uncover the prognosis and immunological characteristics of PGK1 in LUAD. Results: We found that PGK1 mRNA and protein were considerably over-expressed in LUAD compared to normal tissue and that high PGK1 expression is associated with poorer prognostic outcomes in LUAD. The enrichment analysis of PGK1 co-expressed genes in lung adenocarcinoma revealed that PGK1 may be involved in hypoxia, metabolism, DNA synthesis, cell cycle, PI3K/AKT, and various immune and inflammatory signaling pathways. Furthermore, PGK1 is also linked to the recruitment of numerous immune cells, including aDC (dendritic cells), macrophages, and neutrophils. More importantly, PGK1 was highly expressed in immunosuppressive cells, including M2 macrophages, Tregs, and exhausted T cells, among others. Finally, higher PGK1 expression indicated significant correlations to immune checkpoints, TMB (tumor mutation burden), and high response to immunotherapy. Conclusions: The presented findings imply that PGK1, as a glycolysis core gene, may be important for the modification of the immune microenvironment by interacting with the tumor metabolism. The results of this study provide clues for a potential immunometabolic combination therapy strategy in LUAD, for which more experimental and clinical translational research is needed.

Prognostic and immunotherapeutic implications of bilirubin metabolism‐associated genes in lung adenocarcinoma

“…PGK1 serves as a core gene in tumour metabolism, particularly glycolysis, and plays a determining role in evaluating immune therapy response, as indicated by the over-expression of PGK1 in immunosuppressive cells and significant correlations to the expression of ICMs. 31 We explored the somatic mutation landscape in LUAD and delineated key molecular alterations associated with the BMAG-prognostic signature, distinguishing two risk groups with unique molecular profiles. Notably, EIF2AK3 emerged as the most frequently mutated mRNA, characterized predominantly by missense mutations.…”

“…Therefore, augmenting FBP1 expression can be a potential strategy to counteract LUAD progression. PGK1 serves as a core gene in tumour metabolism, particularly glycolysis, and plays a determining role in evaluating immune therapy response, as indicated by the over‐expression of PGK1 in immunosuppressive cells and significant correlations to the expression of ICMs 31 …”

The oncogenic role and regulatory mechanism of PGK1 in human non-small cell lung cancer

“…In recent years, the association between PGK1 and lung cancer has garnered increasing attention. For instance, a meta-analysis has demonstrated that PGK1 affects lung adenocarcinoma prognosis [ 10 ]. Another study has reported a strong correlation between the upregulation of PGK1 and the migratory potential of lung cancer cells [ 11 ].…”