Yang Yuechao, Cui Huanhuan, Li Deheng, Gao Yang, Chen Lei, Zhou Changshuai, Feng Mingtao, Tu Wenjing, Li Sen, Chen Xin, Hao Bin, Li Liangdong, Cao Yiqun
Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cancers (Basel). 2022 Oct 25;14(21):5228. doi: 10.3390/cancers14215228.
: 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. : 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. : 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. : 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.
有氧糖酵解在肿瘤代谢重编程以重塑免疫微环境中起关键作用。磷酸甘油酸激酶1（PGK1）基因编码一种糖酵解酶，可将1,3 - 二磷酸甘油酸转化为3 - 磷酸甘油酸。然而，在肺腺癌（LUAD）中，PGK1在改变肿瘤微环境（TME）中的作用尚未确定。：从多个独立的公共数据集获得了原始数据，包括大量DNA和mRNA测序数据、甲基化修饰数据、单细胞RNA测序数据、蛋白质组学数据、临床病例特征生存数据、免疫治疗数据等。对这些数据进行重新分析以揭示PGK1在LUAD中的预后和免疫特征。：我们发现，与正常组织相比，PGK1 mRNA和蛋白在LUAD中显著过度表达，并且高PGK1表达与LUAD中较差的预后结果相关。肺腺癌中PGK1共表达基因的富集分析表明，PGK1可能参与缺氧、代谢、DNA合成、细胞周期、PI3K/AKT以及各种免疫和炎症信号通路。此外，PGK1还与多种免疫细胞的募集有关，包括aDC（树突状细胞）、巨噬细胞和中性粒细胞。更重要的是，PGK1在免疫抑制细胞中高表达，包括M2巨噬细胞、调节性T细胞和耗竭性T细胞等。最后，较高的PGK1表达表明与免疫检查点、肿瘤突变负荷（TMB）以及对免疫治疗的高反应性存在显著相关性。：所呈现的研究结果表明，PGK1作为糖酵解核心基因，可能通过与肿瘤代谢相互作用对免疫微环境的修饰很重要。本研究结果为LUAD潜在的免疫代谢联合治疗策略提供了线索，为此需要更多的实验和临床转化研究。
