ArticleBMC cancer2025
Epigenetic modifications of the PHOX2A and CDH2 genes expression- new insights into the pathogenesis of multiple myeloma.
Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionMultiple myeloma (MM) is an incurable malignancy that arises from precursory conditions, specifically monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM). The pathogenesis of MM remains largely elusive, particularly in the context of epigenetics. PURPOSE: The aim of this study was to uncover new bioinformatic insights related to the pathogenesis of MM in the context of epigenetic analysis using the NGS method. PATIENTS AND
methodsA total of 60 patients with MM and MGUS were enrolled in the study. Myeloma CD138 + cells were isolated from the collected bone marrow using an immunomagnetic method and used to analyze the DNA methylation profile using the MethylationEPICv2.0 BeadChip Kit. Peripheral blood plasma was used to analyze the expression profile of circulating miRNAs using the miRNAseq method. Additionally, global epigenetic assessment allowed for the selection of several target genes and assessment of their expression using the qRT-PCR method.
resultsOur in-depth analysis allowed us to focus on two genes, PHOX2A and CDH2, which play significant roles in carcinogenesis, and their increased expression is associated with poor prognosis in oncological patients. We observed a decrease in the methylation level associated with these genes in patients with MM compared with those with MGUS, whereas the mRNA expression level was increased. Moreover, among patients with MGUS compared with MM, patients with MGUS presented upregulation of specific miRNAs, namely, miR-208b-3p, and miR-320c, which act as inhibitors of the aforementioned genes.
conclusionsUltimately, identifying genes implicated in the progression of MM may pave the way for the refinement of current treatment protocols or the development of novel therapeutic strategies centred on epigenetic modifications or gene therapies. Additionally, the expression profile of circulating miRNAs may prove useful in selecting molecules that will constitute a good biomarker of disease progression from the preclinical to the fully symptomatic stage.
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