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

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.