Research Paper Volume 15, Issue 22 pp 12927—12951

A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma

Zhijia Zhao1, *, , Xiaochen Shen2, *, , Siqi Zhao1, , Jinhua Wang1, , Yuqin Tian1, , Xiaobo Wang1, , Bo Tang1, ,

  • 1 Department of Hematology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People’s Republic of China
  • 2 Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People’s Republic of China
* Equal contribution and share first authorship

Received: July 7, 2023       Accepted: October 3, 2023       Published: November 15, 2023
How to Cite

Copyright: © 2023 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with diverse clinical and molecular features. Telomere maintenance is widely present in tumors, but there is a lack of relevant reports on the role of telomere-related genes (TRGs) in DLBCL. In this study, we used consensus clustering based on TRGs expression to identify two molecular clusters with distinct prognoses and immune cell infiltration. We developed a TRGs scoring model using univariate Cox regression and LASSO regression in the GSE10846 training cohort. DLBCL patients in the high-risk group had a worse prognosis than those in the low-risk group, as revealed by Kaplan-Meier curves. The scoring model was validated in the GSE10846 testing cohort and GSE87371 cohort, respectively. The high-risk group was characterized by elevated infiltration of activated DCs, CD56 dim natural killer cells, myeloid-derived suppressor cells, monocytes, and plasmacytoid DCs, along with reduced infiltration of activated CD4 T cells, Type 2 T helper cells, γδ T cells, NK cells, and neutrophils. Overexpression of immune checkpoints, such as PDCD1, CD274, and LAG3, was observed in the high-risk group. Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization.


DLBCL: diffuse large B cell lymphoma; TRGs: telomere-related genes; K-M: Kaplan-Meier; COO: cell of origin; GCB: germinal center B-cell; ABC: activated B-cell; R-CHOP: rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; IPI: international prognostic index; RNA: ribonucleic acid; TERT: telomerase reverse transcriptase; TERC: telomerase RNA component; ALT: alternative length of telomeres; HL: hodgkin lymphoma; hTERT: human telomerase; TRGs: telomere-related genes; GEO: Gene Expression Omnibus; LASSO: least absolute shrinkage and selection operator; OS: overall survival; ROC: receiver operating characteristic; RT-qPCR: quantitative real-time PCR; ssGSEA: single-sample Gene Set Enrichment Analysis; DCs: dendritic cells; NK: natural killer; MDSCs: myeloid-derived suppressor cells; AUC: area under the curve; EBV: Epstein-Barr virus; NSCLC: non small-cell lung cancer; TME: tumor microenvironment; PD-L1: programmed cell death ligand 1; AML: acute myeloid leukemia.