Gene expression profiles analysis identifies a novel two-gene signature to predict overall survival in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy, however, specific tumor-associated genes and signaling pathways are yet to be deciphered. Differentially expressed genes (DEGs) were computed based on gene expression profiles from GSE32018, GSE56315, and The Cancer Genome Atlas (TCGA) DLBC. Overlapping DEGs were then evaluated for gene ontology (GO), pathways enrichment, DNA methylation, protein-protein interaction (PPI) network analysis as well as survival analysis. Seventy-four up-regulated and 79 down-regulated DEGs were identified. From PPI network analysis, majority of the DEGs were involved in cell cycle, oocyte meiosis, and epithelial-to-mesenchymal transition (EMT) pathways. Six hub genes including <i>CDC20, MELK, PBK</i>, prostaglandin D2 synthase (<i>PTGDS</i>), <i>PCNA</i>, and <i>CDK1</i> were selected using the Molecular Complex Detection (MCODE). <i>CDC20</i> and <i>PTGDS</i> were able to predict overall survival (OS) in TCGA DLBC and in an additional independent cohort GSE31312. Furthermore, <i>CDC20</i> DNA methylation negatively regulated <i>CDC20</i> expression and was able to predict OS in DLBCL. A two-gene panel consisting of <i>CDC20</i> and <i>PTGDS</i> had a better prognostic value compared with <i>CDC20</i> or <i>PTGDS</i> alone in the TCGA cohort (<i>P</i>=0.026 and 0.039). Overall, the present study identified a set of novel genes and pathways that may play a significant role in the initiation and progression of DLBCL. In addition, <i>CDC20</i> and <i>PTGDS</i> will provide useful guidance for therapeutic applications.