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弥漫性大 B 细胞淋巴瘤的预后免疫风险评分。

A prognostic immune risk score for diffuse large B-cell lymphoma.

机构信息

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

出版信息

Br J Haematol. 2021 Jul;194(1):111-119. doi: 10.1111/bjh.17478. Epub 2021 May 3.

DOI:10.1111/bjh.17478
PMID:33942291
Abstract

We constructed a prognostic score for persons with diffuse large B-cell lymphoma (DLBCL) based on infiltrating immune cells. Data of 956 consecutive subjects were retrieved from the Gene Expression Omnibus database and assigned to training (GSE10846, n = 305) or validation (GSE87371 n = 206 and GSE117556 n = 445 combined) cohorts. Proportions of non-lymphoma cells in the sample were inferred using the ESTIMATE algorithm. An immune risk score was constructed comprised of eight types of non-lymphoma immune cells calculated using the CIBERSORT algorithm. Five-year survival of subjects with an immune risk score ≤ 0·45 in the training cohort was better than that of subjects with a score > 0·45 (hazard ratio [HR] = 3·99; 95% confidence interval [CI] = 2·74, 5·82; P < 0·001). HR in the validation cohort was HR = 2·17 (1·47, 3·21; P < 0·001). Enrichment analyses indicated correlations with genes controlling immune-related biological processes and pathways. A nomogram comprised of the immune risk score and most covariates including age, lactate dehydrogenase concentration (LDH), lymphoma-type (germinal centre B cell [GCB] versus non-GCB), Eastern Cooperative Oncology Group performance status (ECOG-PS) and rituximab therapy had a C-statistic of 0·76 compared with C-statistics of 0·69 and 0·69 for the International Prognostic Index (IPI) and Revised International Prognostic Index (R-IPI). These data indicate the immune risk score is an accurate, independent survival predictor in persons with DLBCL.

摘要

我们基于浸润免疫细胞构建了弥漫性大 B 细胞淋巴瘤(DLBCL)患者的预后评分。从基因表达综合数据库中检索了 956 名连续患者的数据,并将其分配到训练(GSE10846,n=305)或验证(GSE87371 n=206 和 GSE117556 n=445 合并)队列。使用 ESTIMATE 算法推断样本中非淋巴瘤细胞的比例。使用 CIBERSORT 算法计算了由八种非淋巴瘤免疫细胞组成的免疫风险评分。在训练队列中,免疫风险评分≤0.45 的患者的 5 年生存率优于评分>0.45 的患者(风险比 [HR]3.99;95%置信区间 [CI]2.74,5.82;P<0.001)。验证队列中的 HR 为 HR=2.17(1.47,3.21;P<0.001)。富集分析表明与控制免疫相关生物学过程和途径的基因相关。包含免疫风险评分和大多数协变量(包括年龄、乳酸脱氢酶浓度 [LDH]、淋巴瘤类型(生发中心 B 细胞 [GCB]与非-GCB]、东部肿瘤协作组体能状态 [ECOG-PS]和利妥昔单抗治疗)的列线图的 C 统计量为 0.76,而国际预后指数(IPI)和修订后的国际预后指数(R-IPI)的 C 统计量分别为 0.69 和 0.69。这些数据表明,免疫风险评分是 DLBCL 患者准确的独立生存预测指标。

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