High lymphocyte-to-monocyte ratio is associated with low α-fetoprotein expression in patients with hepatitis B virus-associated hepatocellular carcinoma

The association of the peripheral lymphocyte-to-monocyte ratio (LMR) with α-fetoprotein (AFP) status in patients with AFP-positive and AFP-negative hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of the present study was to examine the association between the LMR and AFP status in these patients. The samples were obtained from patients with a hepatitis B virus (HBV) infection, who were negative for non-HBV hepatitis viruses and who did not suffer from autoimmune hepatitis. These patients were retrospectively reviewed and the differences of test indicators in the AFP-negative and AFP-positive groups were assessed. Flow cytometry was used to detect the expression levels of CD4, CD8 and programmed cell death protein 1 (PD-1), and ELISAs were used to analyze the expression levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1. In addition, luciferase reporter assays were used to assess binding of the IL-10 promoter to the glucocorticoid receptor (GR) gene. Receiver operating characteristic curve and Spearman correlation analyses demonstrated that the AFP-negative HCC group exhibited a higher LMR, lower D-dimer and lower fibrin degradation products compared with the AFP-positive HCC group. The cut-off value of the LMR was 2.01 for AFP detection, with a sensitivity of 68.6% and a specificity of 75%. The high LMR noted in the AFP-negative HCC group was accompanied by a lower proportion of CD4(+) T lymphocytes and CD8-PD-1 expression compared with the corresponding levels of these parameters in the AFP-positive HCC group. Furthermore, the high levels of IL-10 and low levels of TGF-β1 were expressed in the AFP-positive HCC group. The data indicated that the IL-10-592 promoter exhibited a potent induction of luciferase activity in 293T cells cotransfected with a GR-overexpressing vector compared with the control cells. However, the relative luciferase activity was not altered following a mutation or polymorphism in the IL-10 gene. These results suggested that a high LMR was indicative of low AFP expression in HBV-associated HCC patients.