Institution of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2021 Oct 22;12:732006. doi: 10.3389/fimmu.2021.732006. eCollection 2021.
The International Prognostic Index (IPI) is widely used to discriminate the 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 therapy, such as immune checkpoint blockade (ICB).
Gene expression data and clinical DLBCL information were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. A total of 371 immune-related genes in DLBCL patients associated with different IPI risk groups were identified by weighted gene co-expression network analysis, and eight genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Subsequently, we analyzed the somatic mutation and transcription profiles of the IPI-IPM subgroups as well as the potential clinical response to immune checkpoint blockade (ICB) in IPI-IPM subgroups.
The IPI-IPM was constructed based on the expression of , , , , , , , and , where high-risk patients had worse overall survival than low-risk patients, consistent with the results in the independent validation cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high and mutation rates, and upregulation of inhibitory immune checkpoints, including , , and , indicating a greater potential response to ICB therapy.
The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms of tumor progression and sheds light on the development of immunotherapy for DLBCL.
国际预后指数(IPI)广泛用于区分弥漫性大 B 细胞淋巴瘤(DLBCL)患者的预后。然而,在靶向治疗的背景下,如免疫检查点阻断(ICB),需要确定新的有价值的生物标志物。
从癌症基因组图谱和基因表达综合数据库中获取基因表达数据和临床 DLBCL 信息。通过加权基因共表达网络分析,确定了与不同 IPI 风险组相关的 371 个与 DLBCL 患者相关的免疫相关基因,并选择了 8 个基因来构建基于 IPI 的免疫预后模型(IPI-IPM)。随后,我们分析了 IPI-IPM 亚组的体细胞突变和转录谱,以及 IPI-IPM 亚组对免疫检查点阻断(ICB)的潜在临床反应。
根据 、 、 、 、 、 、 基因的表达构建了 IPI-IPM,其中高危患者的总生存率低于低危患者,与独立验证队列的结果一致。综合结果表明,高 IPI-IPM 风险评分与免疫相关信号通路、高 和 突变率以及抑制性免疫检查点的上调相关,包括 、 、和 ,表明对 ICB 治疗的潜在反应更大。
IPI-IPM 对 DLBCL 患者具有独立的预后意义,为阐明肿瘤进展的机制提供了免疫学视角,并为 DLBCL 的免疫治疗发展提供了思路。