Expression and clinical significance of CXC chemokine receptors 1 and 2 and CXCL8 in primary hepatocellular carcinoma

Abstract

Objective To investigate the expression and clinical significance of CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) and CXCL8 in peripheral blood mononuclear cells (PBMCs) and liver biopsy tissues from patients with primary hepatocellular carcinoma (PHC). Methods Serum specimens were collected from 36 patients with PHC, 30 patients with liver cirrhosis and 28 healthy subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs. Streptavidin-perosidase (SP) immunohistochemistry was used to detect the expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues. Levels of C-reactive protein (CRP), alpha-fetoprotein (AFP) and ferritin (FER) in the serum specimens were detected by chemiluminescence immunoassay. Then the correlations between these markers were analyzed. Results All of the results showed that the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs from the PHC group were higher than those of the healthy control group (P<0.01) as well as those of the liver cirrhosis group (P<0.05). Up-regulated expression of CXCR1, CXCR2 and CXCL8 in patients with PHC were associated with the depth of tumor invasion, lymph node or distant metastasis, clinical stage and levels of CRP, AFP and FER in serum (P<0.05). The expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues were also significantly increased in the PHC group in comparison with those of the healthy control group as indicated by the result of SP immunohistochemistry (P<0.05). Conclusion Levels of CXCR1, CXCR2 and CXCL8 in the patients with PHC are significantly increased and positively correlated with the levels of AFP, FER and CRP in serum, suggesting that the signal transduction process mediated by CXCR1, CXCR2 and their common ligand CXCL8 may play a key role in the pathological process of PHC. This study may provide a potential new strategy for immune intervention in hepatocellular cancer. Key words: PHC; CXCR1; CXCR2; CXCL8; mRNA; AFP; FER; CRP