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

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.

Keywords: diffuse large B-cell lymphoma; immune target; prognosis; risk score.

Figure 1

Expression of B7-CD28 family genes and risk score distribution in GSE10846 patients. (A) Expression distribution of B7-CD28 family genes. (B) Gene expression scores for all GSE10846 patients plotted in ascending order of risk score. (C) Follow-up and survival of each patient.

Figure 2

Kaplan–Meier curves of overall survival (OS) and progression-free survival (PFS) for high-risk and low-risk GSE10846 (A), GSE31312 (B, C) and GSE117556 (D) patients.

Figure 3

Risk score-related genes and clinical characteristics in GSE10846 patients. Abbreviations: ECOG: Eastern Cooperative Oncology Group score, LDH: lactate dehydrogenase, IPI: International Prognostic Index, ABC: activated B-cell-like, GCB: germinal center B-cell-like, CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone, R-CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab.

Figure 4

Kaplan–Meier curves of overall survival (OS) and progression-free survival (PFS) in high-risk and low-risk GSE10846 (A, B), GSE31312 (C–F), and GSE117556 (G, H) patients with different disease stages.

Figure 5

Kaplan–Meier curves of overall survival (OS) and progression-free survival (PFS) in high-risk and low-risk GSE10846 (A, B), GSE31312 (C–F), and GSE117556 (G, H) patients with different cancer subtypes.

Figure 6

Kaplan–Meier curves of overall survival (OS) in high-risk and low-risk patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (B) or CHOP plus rituximab (R-CHOP) (A, G). Kaplan–Meier curves of overall survival (OS) and PFS in high-risk and low-risk patients with different international prognostic index (IPI) values (C–F, H, I).

Figure 7

Distributions of immune-infiltrating cells in high-risk and low-risk GSE10846 (A), GSE31312 (B), and GSE117556 (C) patients.

Figure 8

Distribution of programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) expression in GSE10846 (A), GSE31312 (B), and GSE117556 (C) patients.

Figure 9. Distribution of immune checkpoint gene expression in GSE10846 patients.