| Background and aimsExportin4(XPO4) is a novel identified candidate tumor-suppressor gene involved in the pathogenesis of primary liver cancer (PLC). In this present study, we aimed to determine the clinical features of XPO4mRNA expression and the DNA promoter methylation status in PBMCs of patients with chronic HBV infection.Patients and MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from this cross-sectional study including44PLC patients,38liver cirrhosis (LC) patients,34chronic hepatitis B (CHB) patients and17healthy controls (HCs). The mRNA level of XPO4in PBMCs was determined by quantitative real time RT-PCR. Meanwhile the CpG island methylation of XP04gene promoter was assessed by methylation specific PCR (MSP).ResultsThe XPO4mRNA level of PLC patients was significantly lower compared with LC and CHB patients as well as HCs (all P<0.01, respectively), and significant differences of the XPO4mRNA level were found in LC and CHB group than HCs (LC vs. HC, P<0.01; CHB vs. HC, P<0.05). Methylation rates of CpG islands in the promoter of XPO4of PLC patients was significantly increased compared to CHB patients and HCs (PLC vs. CHB, P<0.05; PLC vs. HC,P<0.05). Interaction analysis demonstrated that DNA methylation pattern was responsible for the suppression of peripheral XP04transcription in the progression of HBV infection (P=0.000). Furthermore, in PLC patients, AFP level was significantly higher in patients with XPO4methylation than those without methylation((8702±15635)ng/ml vs.(1052±5370) ng/ml, P<0.05), which might provided a new noninvasive method in the detection of primary liver cancer.ConclusionsOur results showed that, transcription of XPO4gene was gradually decreased and methylation rate of XPO4promoter was increased related to progression of HBV infection. In addition, methylation status in PBMCs tended to be a noninvasive biomarker to predict primary liver cancer and the progression of HBV infection. |
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