弥漫性大B细胞淋巴瘤铜死亡与免疫原性细胞死亡联合预后模型的建立与验证
Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.
作者信息
Wang Nana, Shi Shanshan, Li Moran, Yu Xiaoning, Ma Guangxin
机构信息
Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, China.
Department of Geriatrics, Hematology and Oncology Unit, Qilu Hospital of Shandong University, Jinan 250012, China.
出版信息
Aging (Albany NY). 2024 Jan 26;16(2):1218-1236. doi: 10.18632/aging.205399.
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide with a high degree of heterogeneity. Cuproptosis and immunogenic cell death (ICD) have been considered to be vital for tumor progression. However, current understanding of cuproptosis and immunogenic cell death in DLBCL is still very limited. We aim to explore a prognostic model combining cuproptosis and immunogenic cell death in DLBCL.
METHODS
Pearson's correlation analysis was utilized to acquire lncRNAs associated with cuproptosis and immunogenic cell death. Prognostic biomarker identification and model construction involved the use of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. We assessed the predictive capability of the risk model by conducting Kaplan-Meier analysis and time-dependent ROC analysis. The analysis and comparison of immune infiltration and drug sensitivity were conducted in this study. Moreover, RT-qPCR was employed to validate the expression of lncRNAs associated with cuproptosis and immunogenic cell death in DLBCL cell lines.
RESULTS
We identified 4 prognosis-related lncRNAs (ANKRD10-IT1, HOXB-AS1, LINC00520 and LINC01165) that were correlated with cuproptosis and immunogenic cell death. The model was verified to have a good and independent predictive ability in the prognostic prediction of DLBCL patients. Moreover, significant difference was observed in immune infiltration and drug sensitivity between high- and low-risk groups.
CONCLUSION
Our discoveries could enhance the comprehension of the role of cuproptosis and ICD in DLBCL, potentially offering novel viewpoints and knowledge for personalized and precise treatment of DLBCL individuals.
背景
弥漫性大B细胞淋巴瘤(DLBCL)是全球最常见的非霍奇金淋巴瘤类型,具有高度异质性。铜死亡和免疫原性细胞死亡(ICD)被认为对肿瘤进展至关重要。然而,目前对DLBCL中铜死亡和免疫原性细胞死亡的了解仍然非常有限。我们旨在探索一种结合DLBCL中铜死亡和免疫原性细胞死亡的预后模型。
方法
利用Pearson相关性分析获取与铜死亡和免疫原性细胞死亡相关的lncRNA。预后生物标志物的鉴定和模型构建涉及单变量Cox回归、最小绝对收缩和选择算子(LASSO)Cox回归以及多变量Cox回归。我们通过进行Kaplan-Meier分析和时间依赖性ROC分析来评估风险模型的预测能力。本研究进行了免疫浸润和药物敏感性的分析与比较。此外,采用RT-qPCR验证DLBCL细胞系中与铜死亡和免疫原性细胞死亡相关的lncRNA的表达。
结果
我们鉴定出4种与铜死亡和免疫原性细胞死亡相关的预后相关lncRNA(ANKRD10-IT1、HOXB-AS1、LINC00520和LINC01165)。该模型在DLBCL患者的预后预测中被验证具有良好且独立的预测能力。此外,高风险组和低风险组在免疫浸润和药物敏感性方面存在显著差异。
结论
我们的发现可以增强对铜死亡和ICD在DLBCL中作用的理解,可能为DLBCL患者的个性化精准治疗提供新的观点和知识。