Association between lymphoma prognosis and aberrant methylation of ID4 and ZO-1 in bone marrow and paraffin-embedded lymphoma tissues of treatment-naive patients

The aim of the present study was to investigate the association between lymphoma prognosis and aberrant methylation of inhibitor of DNA binding factor 4 (ID4) and tight junction protein 1 (ZO-1) genes in samples isolated from the bone marrow and paraffin-embedded lymphoma tissues of treatment-naive lymphoma patients. The bone marrow biopsy and paraffin-embedded lymphoma tissue samples from treatment-naive lymphoma patients were obtained, along with corresponding control samples from subjects without lymphoma and from lymph nodes of chronic cholecystitis and reactive lymphadenitis patients. Methylation-specific PCR (MSP) reactions were performed to analyze the methylation status on the promoter regions of ID4 and ZO-1. ID4 and ZO-1 promoter regions in the control group were completely unmethylated, whereas the rates of methylation of ID4 and ZO-1 in paraffin-embedded lymphoma tissues of the lymphoma patients were 80.4 and 84.3%, respectively. The methylation positivity rates of both the ID4 or ZO-1 genes in lymphoma patients were 92.2%, which was significantly higher compared to the rates in the control group (0%). The methylation positivity rates of the ID4 and ZO-1 genes in the bone marrow and paraffin-embedded lymphoma tissues of non-Hodgkin lymphoma patients were significantly higher compared to the rates in the Hodgkin lymphoma patients. The survival rate of lymphoma patients with methylated ID4 was significantly lower compared to that of patients with unmethylated ID4. The methylation of the ID4 and ZO-1 genes may be a specific molecular marker for lymphoma diagnosis. The methylation of the ID4 gene may be an indicator of poor prognosis in lymphoma patients.