Association between the expression levels of IL-6 and IL-6R in the hepatocellular carcinoma microenvironment and postoperative recurrence.

Abstract

The tumor microenvironment of hepatocellular carcinoma (HCC) is a complex system, involving mutual promotion and inhibition between cells and molecules. It results in alterations to inflammatory-associated factors, including a decrease in interleukin (IL)-2 and an increase in tumor necrosis factor, together with a characteristic elevation of IL-6. Following the synthesis and release of IL-6, HCC is stimulated through IL-6 binding to the IL-6 receptor (IL-6R). In the present study, immunohistochemistry was performed to investigate the expression levels of IL-6 and IL-6R in 92 patients with HCC, and the association between IL-6/IL-6R expression levels and tumor recurrence was examined. Notably increased expression levels of IL-6 and IL-6R were observed in the HCC microenvironment, and recurrence occurred earlier in patients with high IL-6/IL-6R expression levels compared with those with low expression levels (P<0.05). However, there was no significant difference in overall survival between patients in the two groups (P>0.05). Platelet levels <100×109/l, tumor-node-metastasis stage IIIa and high expression levels of IL-6/IL-6R were independent risk factors for postoperative recurrence (P<0.05). The present study proposed that high IL-6 and IL-6R expression in the HCC microenvironment promotes postoperative tumor recurrence, suggesting that these may be potential predictors of recurrence, and may be used as possible therapeutic targets to enhance the long-term survival of patients.