Microarray-Based Gene Expression Analysis Identifies Potential Diagnostic and Prognostic Biomarkers for Waldenström Macroglobulinemia

Abstract

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.

Single‐cell analysis of MYD88L265P and MYD88WT Waldenström macroglobulinemia patients

“…MAN1A1 gene is located in chromosome 6q and has been found to be commonly affected in WM patients due to the 6q clonal loss. Regarding the FGL2 gene, it has been shown to be highly overexpressed in a subset of WM cases, suggesting that WM cells may be responsive to cytokine signaling through T‐cell receptors 34,35 . From this analysis, we also identified the downregulation of the NEIL1 gene in MYD88 WT patients but not in MYD88 MUT patients.…”

“…Regarding the FGL2 gene, it has been shown to be highly overexpressed in a subset of WM cases, suggesting that WM cells may be responsive to cytokine signaling through T-cell receptors. 34,35 From this analysis, we also identified the downregulation of the NEIL1 gene in MYD88 WT patients but not in MYD88 MUT patients. Furthermore, the ARID5B gene was downregulated in three out of four MYD88 MUT patients and in none of the MYD88 WT patients.…”