Abstract
Background
Diffuse large B-cell lymphoma (DLBCL) is a common and highly aggressive type of lymphoma. Iron metabolism plays a critical role in human diseases, however, which remains completely unclear in patients with DLBCL. The aim is to explore the genetic characteristics and molecular mechanisms underlying iron metabolism in patients with DLBCL.
Methods
Based on the Gene Expression Omnibus (GEO) and the GeneCards database, weighted gene co-expression network analysis (WGCNA) was performed on the DLBCL sample (GSE83632) and Iron metabolism-related datasets. Enrichment analysis(GO/KEGG enrichment analysis and GSEA enrichment analysis) was used to screen the key gene and analyze its expression and possible mechanism of action in patients with DLBCL. The quantitative real-time PCR (qRT-PCR) was used to verify the expression of GATA1 gene.
Results
GATA-binding factor 1 (GATA1), as a key gene of iron metabolism in DLBCL patients, was related to the myeloid cell differentiation and granulocyte differentiation pathways to affect CD4+ T cells, B cells, and monocytes. GATA1 was strongly positively correlated with sensitivity to multiple targeted drugs including imatinib, nilotinib, and crizotinib, but negatively correlated with the PI3K and CDK9 inhibitors. The patients with high GATA1 expression had higher overall survival and better prognosis than the patients with low expression. Additionally, high expression of GATA1 gene was confirmed in DLBCL patients by qRT-PCR analysis.
Conclusions
GATA1 as one of the important genes of iron metabolism suggested a significant biomarker for predicting the prognosis of DLBCL patients.