PCK2 inhibits lung adenocarcinoma tumor cell immune escape through oxidative stress-induced senescence as a potential therapeutic target

[摘要] Background: Our research aimed to better understand how phosphoenolpyruvate carboxykinase 2 (PCK2) is linked to survival outcomes in lung cancer patients. Methods: We confirmed PCK2 expression and its association with the outcome of lung cancer patients using The Cancer Genome Atlas (TCGA) database. PCK2 and immune cell connections were investigated using data from the Tumor IMmune Estimation Resource (TIMER) and TCGA repositories. We used the CancerSEA database to examine the links between PCK2 expression and the efficiency of lung adenocarcinomas, and a T-distributed Stochastic Neighbor Embedding (T-SNE) map was constructed to show the expression profile of PCK2 in single cells in TCGA lung adenocarcinoma samples. The potential mechanism of action was finally investigated using Gene Set Enrichment Analysis (GSEA) enrichment analysis, Gene Ontology (GO) pathway enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: The expression of PCK was lower in lung adenocarcinoma tumor tissues than in paracancerous tissues. Patients with lung adenocarcinoma who expressed PCK2 at high levels fared better in overall survival (OS), disease-specific survival (DSS), and progression free interval (PFI). PCK2 was positively correlated with programmed cell death 1 (PDCD1) expression, and its mutation rate in lung adenocarcinoma was 0.53%. CancerSEA research revealed that in lung adenocarcinoma, PCK2 was negatively correlated with epithelial-mesenchymal transition (EMT) and hypoxia. Gene ontology and KEGG enrichment analysis revealed PCK2-coexpressed genes influenced the onset and progression of lung adenocarcinoma by modulating the activity of DNA-binding transcriptional activators, the specificity of RNA polymerase II, the interaction between neuroactive ligands and their receptors, and the cAMP signaling pathway. The prognosis for lung adenocarcinoma was shown to vary according to whether PCK2 was involved in the response to oxidative stress-induced senescence, gene silencing, cell cycle, and other biological processes. Conclusions: An increased expression of PCK2 may be employed as a novel prognostic biomarker in patients with lung adenocarcinoma and has been shown to increase OS, DSS, and PFI. Improving the prognosis of lung adenocarcinoma by interference with PCK2 may be possible since it induces senescence through the oxidative stress response and blocks the immune escape of tumor cells. These results point to a probable target anticancer treatment development in lung adenocarcinoma.

[学科分类] 呼吸医学

[关键词] Phosphoenolpyruvate carboxykinase 2 (PCK2);lung adenocarcinoma;immune infiltration;gluconeogenesis;prognosis