转录组谱分析揭示了弥漫性大 B 细胞淋巴瘤中具有长期生存预测价值的整合 mRNA-lncRNA 特征。

Transcriptome profiling reveals an integrated mRNA-lncRNA signature with predictive value for long-term survival in diffuse large B-cell lymphoma.

机构信息

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.

Department of Pathology, Shanxi Cancer Hospital, Taiyuan 030013, China.

出版信息

Aging (Albany NY). 2020 Nov 18;12(22):23275-23295. doi: 10.18632/aging.104100.

Abstract

For patients with diffuse large B-cell lymphoma (DLBCL), survival at 24 months is a milestone for long-term survival. The purpose of this study was to develop a multigene risk score (MGRS) to refine the International Prognostic Index (IPI) model to identify patients with DLBCL at high risk of death within 24 months. Using a robust statistical strategy, we built a MGRS incorporating nine mRNAs and two lncRNAs. Stratification and multivariable Cox regression analysis confirmed the MGRS as an independent risk factor. A nomogram based on IPI+MGRS model was constructed and its calibration plot showed close agreement between predicted 2-year survival rate and observed rate. The 2-year AUC was bigger with the IPI+MGRS model (ΔAUC=0.162; 95%CI 0.1295-0.1903) than with the IPI model, and the IPI+MGRS model more accurately predicted the prognostic risk of DLBCL. The 2-year survival decision curve revealed the IPI+MGRS model was more useful clinically than the IPI model. Functional enrichment analysis showed that the MGRS correlated with cell cycle, DNA replication and repair. The results were validated using an independent external dataset. In conclusion, we successfully developed an integrated mRNA-lncRNA signature to refine the IPI model for predicting long-term survival of patients with DLBCL.

摘要

对于弥漫性大 B 细胞淋巴瘤(DLBCL)患者,24 个月的生存率是长期生存的一个重要里程碑。本研究旨在开发一种多基因风险评分(MGRS),以完善国际预后指数(IPI)模型,从而识别出 24 个月内死亡风险较高的 DLBCL 患者。我们采用稳健的统计策略,构建了一个包含 9 个 mRNAs 和 2 个 lncRNAs 的 MGRS。分层和多变量 Cox 回归分析证实,MGRS 是死亡的独立风险因素。我们构建了一个基于 IPI+MGRS 模型的列线图,其校准图显示预测的 2 年生存率与观察到的生存率之间具有很好的一致性。与 IPI 模型相比,加入 MGRS 的 IPI+MGRS 模型的 2 年 AUC 更大(ΔAUC=0.162;95%CI 0.1295-0.1903),并且更准确地预测了 DLBCL 的预后风险。2 年生存决策曲线表明,与 IPI 模型相比,IPI+MGRS 模型在临床上更有用。功能富集分析表明,MGRS 与细胞周期、DNA 复制和修复有关。该结果通过独立的外部数据集得到了验证。总之,我们成功开发了一种综合的 mRNA-lncRNA 特征,以完善 IPI 模型,从而预测 DLBCL 患者的长期生存。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dea/7746345/e330bf16e790/aging-12-104100-g001.jpg

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