Decreased IL-37 expression in hepatocellular carcinoma tissues and liver cancer cell lines

The role of IL-37 in cancer is currently largely unknown. The present study aimed to investigate IL-37 expression in hepatocellular carcinoma (HCC), paracancerous tissues (PT) and liver cancer cell lines, and their associations between IL-37 and NF-kappa B. A total of 65 HCC and 65 PT tissues were collected. The expression of IL-37 and NF-kappa B in tissues was detected by immunohistochemistry (IHC) and the data was analyzed using SPSS software. In the in vitro studies, IL-37 gene was transfected into HepG2 and MHCC97H cell lines with Lipofectamine 3000, and the protein regulation of NF-kappa B by IL-37 was verified by immunofluorescence (IF) and western blotting. In HCC, the positive expression rates of IL-37 and NF-kB were 21.5 and 95.4%, respectively. In PT, strong positive staining of IL-37and weak positive staining of NF-kappa B were observed. The normal expression levels of IL-37 and NF-kappa B, the increased IL-37 and decreased NF-kappa B induced by IL-37 gene transfection were observed through IF in cell lines. In terms of clinical significance, the difference in IL-37 expression between HCC and PT was statistically significant (chi(2)=55.05; P<0.001). IL-37 expression in HCC but not PT was negatively associated with serum AFP (chi(2)=6.522; P=0.039). IL-37 expression in PT was associated with sex (chi(2)=13.12; P=0.003) and tumor size (chi(2)=7.996; P=0.045). NF-kappa B expression in PT was associated with age, sex and BCLC stage. Notably, there was a negative correlation between IL-37 and NF-kappa B in HCC (r=-0.277; P=0.029) but not in PT (P>0.05). IL-37 overexpression downregulated the NF-kappa B protein by 56.50% in HepG2 cells (P<0.05) and 30.52% in MHCC97H cells (P<0.05). In conclusion, the expression of IL-37 in HCC and PT was specifically associated with serum AFP and tumor size, respectively. IL-37 expression was negatively correlated with NF-kappa B protein expression in HCC tissues and liver cancer cell lines.