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. 2020 May 5:737:144445.
doi: 10.1016/j.gene.2020.144445. Epub 2020 Feb 5.

Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma

Hongsheng Guo  1 , Peng Li  1 , Liudan Su  2 , Kun Wu  2 , Kai Huang  3 , Ruizhi Lai  3 , Jing Xu  3 , Dingbao Sun  3 , Shuxian Li  1 , Ziliang Deng  1 , Yan Wang  1 , Haina Guo  4 , Zhangquan Chen  2 , Sen Wang  5
Affiliations

Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma

Hongsheng Guo et al. Gene. .

Abstract

Objective: The function of IL-37 in cancer remains largely unclear. The present research was to probe the protein expression of IL-37 and Oct4 in hepatocellular carcinoma (HCC), para-cancerous tissues (PT) and cancer cell lines, and discuss their relationship.

Methods: Forty-nine HCC specimens and forty-nine PT samples were collected for immunohistochemical staining of IL-37 and Oct4 protein. Then, the correlations among IL-37, Oct4 and the clinical indicators were analyzed. In further in vitro studies, IL-37 was over expressed in HepG2 and MHCC97H cancer cell lines by gene transfection using a lipo3000 kit. Finally, the protein expression of IL-37 and Oct4 was detected by immunofluorescence and western blot to verify the in vivo correlation between IL and 37 and Oct4.

Results: In HCC, IL-37 protein expression was weakly positive with a positive rate of 12.2% while Oct4 expression was strongly positive with a positive rate of 91.8%. In PT, strong positive IL-37 (83.7%) and weakly positive Oct4 (91.8%) were shown. The increased IL-37 and decreased Oct4 induced by IL-37 gene transfection were observed through IF in cells. In terms of clinical significance, the difference of IL-37 expression between HCC and PT was statistically significant (χ2 = 51.815, P = 3.2796 × 10-11). IL-37 in tumor tissues was associated with serum AFP (χ2 = 5.515, P = 0.048) and cirrhosis (χ2 = 7.451, P = 0.014). IL-37 expression of PT was link to gender (χ2 = 10.376, P = 0.013) and tumor size (χ2 = 8.118, P = 0.04). The expression of Oct4 in HCC was related to the patient's gender and cirrhosis. Importantly, there was a negative correlation between IL and 37 and Oct4 in tumor tissues (r = -0.299, P = 0.047) but not in PT (P > 0.05). Oct4 protein expression was down-regulated by IL-37 by 63.35% in HepG2 cells (P < 0.05) and 95.20% in MHCC97H cells (P < 0.05).

Conclusion: IL-37 expression in tumor tissues and PT was related to serum AFP and liver cirrhosis, tumor size, respectively. IL-37 protein expression was correlated with Oct4 in cancer cell lines and tumor tissues but not PT. The present study indicated that IL-37 might play a role in the development of HCC.

Keywords: AFP; Hepatocellular carcinoma; IL-37; Oct4.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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