Research Paper Volume 11, Issue 12 pp 3939—3957

B7-CD28 gene family expression is associated with prognostic and immunological characteristics of diffuse large B-cell lymphoma

Gangjian Wang 1, *, , Xiaorui Fu 1, *, , Yu Chang 1, , Xin Li 1, , Xiaolong Wu 1, , Ling Li 1, , Lei Zhang 1, , Zhenchang Sun 1, , Xudong Zhang 1, , Mingzhi Zhang 1, ,

  • 1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
* Equal contribution

received: April 21, 2019 ; accepted: June 9, 2019 ; published: June 13, 2019 ;

https://doi.org/10.18632/aging.102025
How to Cite

Copyright: Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The B7-CD28 gene family plays a key role in regulating cellular immunity and is closely related to tumorigenesis and immune evasion. Here, we explored associations between clinical and immune features and B7-CD28 gene family expression in Gene Expression Omnibus (GEO) datasets representing 1812 diffuse large B-cell lymphoma (DLBCL) patients. This included 414 in the GSE10846 training cohort and 470 and 928 patients in the GSE31312 and GSE117556 validation cohorts, respectively. Four survival-associated genes identified in the GSE10846 cohort by univariate Cox analysis were incorporated into a multivariate analysis, ultimately establishing a three-gene risk signature. Risk scores assigned based on expression of these genes were validated by Kaplan–Meier and multivariable Cox analyses in the remaining datasets and in important clinical subsets. High-risk patients had shorter overall survival and, in some cases, progression-free survival than low-risk patients. Additionally, expression of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), as well as several other important immune checkpoint genes, differed between high-risk and low-risk patients, as did the proportions of various immune-infiltrating cells. Finally, further analysis confirmed that these B7-CD28 genes play important roles in immune responses altered in DLBCL.

Abbreviations

DLBCL: diffuse large B-cell lymphoma; GEO: Gene Expression Omnibus; PD-1: programmed cell death 1; PD-L1: programmed death ligand 1; APCs: antigen-presenting cells; OS: overall survival; HR: hazard ratio; CI: confidence interval; PFS: progression-free survival; R-CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone; IPI: International Prognostic Index; GO: gene ontology; Tregs: regulatory T cells; Th1: T helper cell 1; Th2: T helper cell 2.