背景:乳糖化,新发现的涉及乳酸的PTM,与实体瘤的增殖和转移有关。淋巴瘤患者表现出高乳酸水平,然而,乳酸化在淋巴瘤中的作用尚未得到充分研究。本研究旨在使用肿瘤数据库鉴定淋巴瘤中与乳酸相关的基因,并通过细胞实验和临床标本评估其对患者预后的预测价值。
方法:使用TCGA和GEO数据集,我们分析了弥漫性大B细胞淋巴瘤患者中与乳酸相关的基因表达水平.我们还评估了乳酸化基因风险评分的预后意义,探讨其对药物敏感性和肿瘤免疫功能的影响。通过细胞实验和小鼠体内实验鉴定和功能验证了影响乳酸化的关键基因。此外,在临床标本中检查了乳酸化与淋巴瘤预后之间的关系.
结果:我们从与乳酸化相关的基因集中鉴定了70个与弥漫性大B细胞淋巴瘤预后相关的基因。使用临床数据和COX回归算法,我们建立了优化的乳酸化Riskscore模型.该模型与预后显着相关,并显示出免疫细胞浸润的差异,特别是巨噬细胞。高危患者对化疗药物表现出耐药性,但对免疫疗法反应良好。HNRNPH1,一个与乳酸相关的基因,影响患者预后,凋亡,淋巴瘤细胞的细胞周期分布,和小鼠的肿瘤体积。在淋巴瘤标本中,与Bcl-2,C-myc,P53水平
结论:乳糖化影响弥漫性大B细胞淋巴瘤的预后,肿瘤免疫功能,和抗药性。我们基于乳酸化的Riskscore模型有助于患者分层和治疗选择。HNRNPH1调节乳酸化,从而影响患者预后。
BACKGROUND: Lactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation\'s role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens.
METHODS: Using TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens.
RESULTS: We identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels.
CONCLUSIONS: Lactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.