Zhu Miao, Xiao Qin, Cai Xinzhen, Chen Zhiyue, Shi Qingqing, Sun Xing, Xie Xiaoyan, Sun Mei
Department of Hematology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State, Administration of Traditional Chinese Medicine, Yangzhou University, Yangzhou 225001, China; Yangzhou Hematology Laboratory, Yangzhou 225001, China.
Department of Pathology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou 225001, China.
Transl Oncol. 2024 Nov;49:102102. doi: 10.1016/j.tranon.2024.102102. Epub 2024 Aug 14.
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.
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.
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.
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.
乳酰化是一种新发现的涉及乳酸的蛋白质翻译后修饰，与实体瘤的增殖和转移有关。淋巴瘤患者乳酸水平较高，但乳酰化在淋巴瘤中的作用尚未得到充分研究。本研究旨在利用肿瘤数据库鉴定淋巴瘤中与乳酰化相关的基因，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。
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酰化相关基因的表达水平。我们还评估了乳酰化基因风险评分的预后意义，探讨了它们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并功能验证了关键的乳酰化影响基因。此外，在临床标本中检测了乳酰化与淋巴瘤预后的关系。
我们从与乳酰化相关的基因集中鉴定出70个与弥漫性大B细胞淋巴瘤预后相关的基因。利用临床数据和COX回归算法，我们开发了一个优化的乳酰化风险评分模型。该模型与预后显著相关，并在免疫细胞浸润方面表现出差异，尤其是巨噬细胞。高危患者对化疗药物耐药，但对免疫治疗反应良好。一种与乳酰化相关的基因HNRNPH1影响患者预后、淋巴瘤细胞的凋亡、细胞周期分布以及小鼠肿瘤体积。在淋巴瘤标本中，乳酰化水平与Bcl-2、C-myc和P53水平相关。
乳酰化影响弥漫性大B细胞淋巴瘤的预后、肿瘤免疫功能和耐药性。我们基于乳酰化的风险评分模型有助于患者分层和治疗选择。HNRNPH1调节乳酰化，从而影响患者预后。
