Department of Hematology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
Team of Neonatal & Infant Development, Health and Nutrition, NDHN. School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China.
Apoptosis. 2024 Oct;29(9-10):1454-1465. doi: 10.1007/s10495-024-01996-9. Epub 2024 Jul 15.
Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.
铜蛋白相关基因 (CRGs) 已被证明是 2019 年冠状病毒病 (COVID-19) 和癌症的潜在治疗靶点,但它们在弥漫性大 B 细胞淋巴瘤 (DLBC/DLBCL) 患者 COVID-19 感染中的免疫和分子机制很少被报道。我们的研究目标首先是通过单变量分析、机器学习和临床样本筛选 COVID-19 中的关键 CRGs。其次,我们通过泛癌分析确定关键 CRGs 在 DLBCL 中的表达和预后作用。我们使用多个数据集和独立的临床样本验证了关键 CRGs 的表达水平和预后,并通过细胞实验验证了关键 CRGs 在 DLBCL 中的功能作用。最后,我们验证了 COVID-19 感染的 DLBCL 患者样本中 CRGs 的表达水平,并分析了它们在 COVID-19 和 DLBCL 中的共同途径。结果表明,突触核蛋白-α (SNCA) 是 COVID-19 和 DLBCL 的共同关键差异基因。DLBCL 细胞证实,SNCA 的高表达可显著促进细胞凋亡,并显著抑制 DLBCL 的周期进程。SNCA 的高表达可以通过调节树突状细胞的免疫浸润来调节主要组织相容性复合物 (MHCs) 和 T 细胞受体 (TCR) 的结合,有效增强 T 细胞介导的抗肿瘤免疫并清除癌细胞。总之,SNCA 可能是 DLBCL 患者 COVID-19 感染的潜在治疗靶点。我们的研究为提高 DLBCL 患者 COVID-19 感染的临床治疗提供了理论依据。