Liu Tingting, Kong Xiangrui, Wei Jianshe
Institute for Brain Sciences Research, School of Life Sciences, Henan University, Kaifeng 475004, China.
Curr Issues Mol Biol. 2024 Sep 12;46(9):10038-10064. doi: 10.3390/cimb46090600.
Recent studies have uncovered intriguing connections between Parkinson's disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise. This has sparked our interest in exploring common molecular mechanisms and genetic factors that may be involved in the relationship between neurodegenerative diseases and tumorigenesis. The Gene4PD database was used to retrieve PD differentially expressed genes (DEGs), the biological functions of differential expression disulfidptosis-related genes (DEDRGs) were analyzed, the ROCs of DEDRGs were analyzed using the GEO database, and the expression of DEDRGs was verified by an MPTP-induced PD mouse model in vivo. Then, the DEDRGs in more than 9000 samples of more than 30 cancers were comprehensively and systematically characterized by using multi-omics analysis data. In PD, we obtained a total of four DEDRGs, including , , , and . The enriched biological functions include the regulation of the NF-κB signaling pathway, mitochondrial function, apoptosis, and tumor necrosis factor, and these genes are rich in different brain regions. In the MPTP-induced PD mouse model, the expression of ACTB was decreased, while the expression of ACTN4, INF2, and MYL6 was increased. In pan-cancer, the high expression of ACTB, ACTN4, and MYL6 in GBMLGG, LGG, MESO, and LAML had a poor prognosis, and the high expression of INF2 in LIHC, LUAD, UVM, HNSC, GBM, LAML, and KIPAN had a poor prognosis. Our study showed that these genes were more highly infiltrated in Macrophages, NK cells, Neutrophils, Eosinophils, CD8 T cells, T cells, T helper cells, B cells, dendritic cells, and mast cells in pan-cancer patients. Most substitution mutations were G-to-A transitions and C-to-T transitions. We also found that miR-4298, miR-296-3p, miR-150-3p, miR-493-5p, and miR-6742-5p play important roles in cancer and PD. Cyclophosphamide and ethinyl estradiol may be potential drugs affected by DEDRGs for future research. This study found that , , , and are closely related to PD and pan-cancer and can be used as candidate genes for the diagnosis, prognosis, and therapeutic biomarkers of neurodegenerative diseases and cancers.
最近的研究揭示了帕金森病（PD）与癌症之间令人感兴趣的联系，这两种疾病看似属于不同的类别。双硫死亡作为一种新型的程序性细胞死亡形式已受到关注，它与包括神经退行性疾病和癌症在内的各种病理状况有关。双硫死亡涉及细胞内氧化还原稳态的失调，导致二硫键积累并随后引起细胞死亡。这激发了我们探索可能参与神经退行性疾病与肿瘤发生关系的共同分子机制和遗传因素的兴趣。利用Gene4PD数据库检索PD差异表达基因（DEG），分析差异表达的双硫死亡相关基因（DEDRG）的生物学功能，使用GEO数据库分析DEDRG的ROC曲线，并通过MPTP诱导的PD小鼠模型在体内验证DEDRG的表达。然后，利用多组学分析数据对30多种癌症的9000多个样本中的DEDRG进行了全面系统的表征。在PD中，我们总共获得了四个DEDRG，包括 、 、 和 。富集的生物学功能包括对NF-κB信号通路、线粒体功能、细胞凋亡和肿瘤坏死因子的调节，并且这些基因在不同脑区中丰富表达。在MPTP诱导的PD小鼠模型中，ACTB的表达降低，而ACTN4、INF2和MYL6的表达增加。在泛癌中，ACTB、ACTN4和MYL6在多形性胶质母细胞瘤（GBMLGG）、低级别胶质瘤（LGG）、间皮瘤（MESO）和急性髓系白血病（LAML）中的高表达预后较差，而INF2在肝细胞癌（LIHC）、肺腺癌（LUAD）、葡萄膜黑色素瘤（UVM）、头颈部鳞状细胞癌（HNSC）、胶质母细胞瘤（GBM）、LAML和胰腺导管腺癌（KIPAN）中的高表达预后较差。我们的研究表明，这些基因在泛癌患者的巨噬细胞、自然杀伤细胞、中性粒细胞、嗜酸性粒细胞、CD8 T细胞、T细胞、辅助性T细胞、B细胞、树突状细胞和肥大细胞中浸润程度更高。大多数替换突变是G到A的转变和C到T的转变。我们还发现miR-4298、miR-296-3p、miR-150-3p、miR-493-5p和miR-6742-5p在癌症和PD中发挥重要作用。环磷酰胺和炔雌醇可能是未来研究中受DEDRG影响的潜在药物。本研究发现 、 、 和 与PD和泛癌密切相关，可作为神经退行性疾病和癌症诊断、预后及治疗生物标志物的候选基因。
