MIF promoter polymorphism increases peripheral blood expression levels, contributing to increased susceptibility and poor prognosis in hepatocellular carcinoma

摘要

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood.