Identification and validation of hub genes in CD5-positive diffuse large B-cell lymphoma

Abstract

CD5+ diffuse large B-cell lymphoma (DLBCL), as a significant heterogeneity category of DLBCL, is reflected in both the molecular biological and genetic levels, which in turn induces ever-changing clinical manifestations, and what mediates tumor survival mechanisms are still unclear. This study aimed to predict the potential hub genes in CD5+ DLBCL. A total of 622 patients with DLBCL diagnosed between 2005 and 2019 were included. High expression of CD5 was correlated with IPI, LDH, and Ann Arbor stage, patients with CD5-DLBCL have longer overall survival. We identified 976 DEGs between CD5-negative and positive DLBCL patients in the GEO database and performed GO and KEGG enrichment analysis. After intersecting the genes obtained through the Cytohubba and MCODE, further external verification was performed in the TCGA database. Three hub genes were screened: VSTM2B, GRIA3, and CCND2, of which CCND2 were mainly involved in cell cycle regulation and JAK-STAT signaling pathways. Analysis of clinical samples showed that the expression of CCND2 was found to be correlated with CD5 (p = 0.001), and patients with overexpression of CCND2 in CD5+ DLBCL had poor prognosis (p = 0.0455). Cox risk regression analysis showed that, for DLBCL, CD5, and CCND2 double positive was an independent poor prognostic factor (HR: 2.545; 95% CI: 1.072–6.043; p = 0.034). These findings demonstrate that CD5 and CCND2 double-positive tumors should be stratified into specific subgroups of DLBCL with poor prognosis. CD5 may regulate CCND2 through JAK-STAT signaling pathways, mediating tumor survival. This study provides independent adverse prognostic factors for risk assessment and treatment strategies for newly diagnosed DLBCL.