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An IPI based immune prognostic model for diffuse large B-cell lymphoma
bioRxiv - Bioinformatics Pub Date : 2021-05-29 , DOI: 10.1101/2021.03.03.433839
Shidai Mu , Deyao Shi , Lisha Ai , Fengjuan Fan , Fei Peng , Chunyan Sun , Yu Hu

Background: International Prognostic Index (IPI) was widely used to better discriminate prognosis of patients with diffuse large B-cell lymphoma (DLBCL) . However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapies, such as immune checkpoint blockade (ICB) therapy. Methods: Gene expression data and clinical information of DLBCL were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. 371 immune-related hub genes in DLBCL patients with different IPI levels were identified by weighted gene co-expression network analysis (WGCNA), and 8 genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Afterward, the genetic, somatic mutational and molecular profiles of IPI-IPM subgroups were analyzed, as well as the potential clinical response of ICB in different IPI-IPM subgroups. Results: The IPI-IPM was constructed based on the expression of CMBL, TLCD3B, SYNDIG1, ESM1, EPHA3, HUNK, PTX3 and IL12A, where high-risk patients had shorter overall survival (OS) than low-risk patients, consistent with the results in the GEO cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, as well as up-regulation of inhibitory immune checkpoints including PD-L1, BTLA and SIGLEC7, indicating more potential response to ICB therapy. Conclusion: The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms on tumor progression, also sheds a light on developing immunotherapy for DLBCL.

中文翻译:

基于 IPI 的弥漫性大 B 细胞淋巴瘤免疫预后模型

背景:国际预后指数(IPI)被广泛用于更好地区分弥漫性大 B 细胞淋巴瘤(DLBCL)患者的预后。然而,在靶向治疗(例如免疫检查点阻断 (ICB) 治疗)的背景下,非常需要确定新的有价值的生物标志物。方法:DLBCL的基因表达数据和临床信息来自癌症基因组图谱(TCGA)和基因表达综合(GEO)数据集。通过加权基因共表达网络分析(WGCNA)鉴定了不同IPI水平的DLBCL患者的371个免疫相关枢纽基因,从中筛选出8个基因构建基于IPI的免疫预后模型(IPI-IPM)。然后,分析了 IPI-IPM 亚群的遗传、体细胞突变和分子谱,以及 ICB 在不同 IPI-IPM 亚组中的潜在临床反应。结果:基于CMBL、TLCD3B、SYNDIG1、ESM1、EPHA3、HUNK、PTX3和IL12A的表达构建IPI-IPM,其中高危患者的总生存期(OS)短于低危患者,与结果在 GEO 队列中。综合结果表明,高 IPI-IPM 风险评分与免疫相关信号通路、高 KMT2D 和 CD79B 突变率以及包括 PD-L1、BTLA 和 SIGLEC7 在内的抑制性免疫检查点的上调相关,表明更多的潜在反应到 ICB 治疗。结论:IPI-IPM对DLBCL患者具有独立的预后意义,为阐明肿瘤进展机制提供了免疫学视角,
更新日期:2021-05-30
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