Role of IL-33 expression in oncogenesis and development of human hepatocellular carcinoma

Interleukin-33 (IL-33), a newly-discovered cytokine belonging to the IL-1 family, serves an important role in inflammation. However, it is not clear whether IL-33 is of clinical significance in hepatocarcinogenesis. The present study was designed to investigate the role of IL-33 during oncogenesis and development of hepatocellular carcinoma (HCC). IL-33 protein expression was detected in 76 HCC (including 36 para-carcinoma), 33 cirrhosis, 30 hepatitis, and 20 normal liver tissues using immunohistochemistry. IL-33 mRNA expression in carcinoma and para-carcinoma tissues was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The possible correlation between IL-33 and clinicopathological parameters of HCC was also analyzed. Significant differences in IL-33 expression were not observed among normal, hepatic, and cirrhotic tissues (P>0.05), whereas the level of protein positive rate was markedly reduced in HCC tissues (P<0.01). Positive staining of IL-33 in non-cancerous liver (NCL) tissues (i.e. normal, hepatitis, and liver cirrhosis) was located predominantly in the nucleus and occasionally in the cytoplasm of hepatocytes; however, the expression in HCC tissues was mostly restricted to the cytoplasm. A significant alteration in protein localization was observed in HCC tissues as compared with NCL tissues (P<0.01). In comparison with HCC tissues, cytoplasmic staining of IL-33 was increased in para-carcinoma tissues. RT-PCR assay further confirmed relatively high mRNA expression levels of IL-33 in para-carcinoma tissues. IL-33 expression was significantly negatively associated with tumor histological grade (r=-0.279, P=0.015), but not with year, gender, tumor size, clinical stage, HCC with hepatitis and cirrhosis background, lymph node metastasis or intrahepatic vascular embolism (P>0.05). Therefore, the aberrant expression of IL-33 is associated with oncogenesis and progression of HCC and the cytoplasmic accumulation of the protein may serve a role in hepatocarcinogenesis.