Integrated bioinformatics analysis reveals dynamic candidate genes and signaling pathways involved in the progression and prognosis of diffuse large B-cell lymphoma

Abstract

Background Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined. Aim We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prognosis of DLBCL. Methods We retrieved the raw gene expression profile and clinical information of GSE12453 from the Gene Expression Omnibus (GEO) database. We used integrated bioinformatics analysis to identify differentially co-expressed genes. The CIBERSORT analysis was also applied to predict tumor-infiltrating immune cells (TIICs) in the GSE12453 dataset. We performed survival and ssGSEA (single-sample Gene Set Enrichment Analysis) (for TIICs) analyses and validated the hub genes using GEPIA2 and an independent GSE31312 dataset. Results We identified 46 differentially co-expressed hub genes in the GSE12453 dataset. Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes. The core genes prognostic values and expression levels were further validated in the GEPIA2 database and GSE31312 dataset to be reliable (p < 0.01). The core genes’ main KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichments were Ribosome and Coronavirus disease-COVID-19. High expressions of the 15 core hub genes had prognostic value in DLBCL. The core genes showed significant predictive accuracy in distinguishing DLBCL cases from non-tumor controls, with the area under the curve (AUC) ranging from 0.992 to 1.00. Finally, CIBERSORT analysis on GSE12453 revealed immune cells, including activated memory CD4+ T cells and M0, M1, and M2-macrophages as the infiltrates in the DLBCL microenvironment. Conclusion Our study found differentially co-expressed core hub genes and relevant pathways involved in ribosome and COVID-19 disease that may be potential targets for prognosis and novel therapeutic intervention in DLBCL.