Alaseem Ali M, Aldali Jehad A, Alasiri Glowi, Alhujaily Muhanad, AlHussaini Khalid I, AlKhamees Osama A
Department of Pharmacology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Front Oncol. 2025 Jul 14;15:1610886. doi: 10.3389/fonc.2025.1610886. eCollection 2025.
Metabolic reprogramming within the tumor microenvironment significantly affects cancer progression by shifting toward aerobic glycolysis and lactate production, while also supporting mitochondrial oxidative phosphorylation. The glyoxalase system, comprising GLO-1 and GLO-2, maintains metabolic homeostasis by neutralizing methylglyoxal (MG) byproducts. GLO-1 protects cells from damage by detoxifying MG via glutathione. In the curent study, pan-cancer analysis revealed elevated GLO-1 mRNA levels across various malignancies, exhibiting variable prognostic implications on patient survival: reduced survival in ACC, MESO, and SARC, and enhanced survival in KIRC and LIHC. GLO-1 activity is regulated by transcriptional and post-translational modifications, including phosphorylation, NO-mediated modification, and glutathionylation. The role of GLO-1 in survival and disease course differs depending on the specific cancer. GLO-1 levels were associated with immunotherapy markers like microsatellite instability (MSI) and tumor mutational burden (TMB), with positive correlations between GLO-1 and MSI in UCEC, TGCT, and STAD, and between GLO-1 and TMB in LUAD, UCEC, LIHC, MESO, SKCM, and READ. In terms of immune cell presence, GLO-1 was associated with increased endothelial and neutrophil cells, decreased T and B cell populations, and increased activated CD4 T cells, memory B cells, and type 2 helper T cells. In summary, our study highlights GLO-1 as a significant biomarker across multiple cancers that plays a key role in cancer progression, immune modulation, and therapeutic response.
肿瘤微环境中的代谢重编程通过向有氧糖酵解和乳酸生成转变，显著影响癌症进展，同时也支持线粒体氧化磷酸化。由GLO-1和GLO-2组成的乙二醛酶系统通过中和甲基乙二醛（MG）副产物来维持代谢稳态。GLO-1通过谷胱甘肽使MG解毒，从而保护细胞免受损伤。在本研究中，泛癌分析显示，在各种恶性肿瘤中GLO-1 mRNA水平升高，对患者生存具有不同的预后意义：在ACC、MESO和SARC中生存率降低，而在KIRC和LIHC中生存率提高。GLO-1活性受转录和翻译后修饰的调节，包括磷酸化、NO介导的修饰和谷胱甘肽化。GLO-1在生存和疾病进程中的作用因具体癌症而异。GLO-1水平与微卫星不稳定性（MSI）和肿瘤突变负担（TMB）等免疫治疗标志物相关，在UCEC、TGCT和STAD中，GLO-1与MSI呈正相关，在LUAD、UCEC、LIHC、MESO、SKCM和READ中，GLO-1与TMB呈正相关。在免疫细胞存在方面，GLO-1与内皮细胞和中性粒细胞增加、T细胞和B细胞群体减少以及活化的CD4 T细胞、记忆B细胞和2型辅助性T细胞增加有关。总之，我们的研究强调GLO-1是多种癌症中的重要生物标志物，在癌症进展、免疫调节和治疗反应中起关键作用。
