An integrated regulatory network based on comprehensive analysis of mRNA expression, gene methylation and expression of long non-coding RNAs (lncRNAs) in myelodysplastic syndromes

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.