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

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

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.

Keywords: diffuse large B-cell lymphoma; long-term survival; mRNA-lncRNA signature; predictive accuracy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Databases, Genetic
  • Decision Support Techniques*
  • Gene Expression Profiling*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Nomograms*
  • Predictive Value of Tests
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Messenger