Department of Histology and Embryology of the Basic Medical College, Guangdong Medical University, Dongguan, Guangdong Province 523808, China.
Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong Province 523808, China.
Gene. 2020 May 5;737:144445. doi: 10.1016/j.gene.2020.144445. Epub 2020 Feb 5.
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.
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.
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 (χ = 51.815, P = 3.2796 × 10). IL-37 in tumor tissues was associated with serum AFP (χ = 5.515, P = 0.048) and cirrhosis (χ = 7.451, P = 0.014). IL-37 expression of PT was link to gender (χ = 10.376, P = 0.013) and tumor size (χ = 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).
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.
IL-37 在癌症中的功能尚不清楚。本研究旨在探讨白细胞介素-37（IL-37）和 Oct4 在肝细胞癌（HCC）、癌旁组织（PT）和癌细胞系中的蛋白表达情况，并探讨它们之间的关系。
收集 49 例 HCC 标本和 49 例 PT 标本，进行 IL-37 和 Oct4 蛋白的免疫组织化学染色。然后，分析 IL-37、Oct4 与临床指标的相关性。进一步的体外研究中，采用 lipo3000 试剂盒转染基因，使 HepG2 和 MHCC97H 癌细胞系过表达 IL-37。最后，通过免疫荧光和 Western blot 检测 IL-37 和 Oct4 的蛋白表达，验证体内 IL-37 和 Oct4 之间的相关性。
在 HCC 中，IL-37 蛋白表达呈弱阳性，阳性率为 12.2%，而 Oct4 表达呈强阳性，阳性率为 91.8%。在 PT 中，IL-37 呈强阳性（83.7%），Oct4 呈弱阳性（91.8%）。通过细胞内免疫荧光观察到 IL-37 基因转染诱导的 IL-37 增加和 Oct4 减少。从临床意义来看，HCC 和 PT 之间的 IL-37 表达差异具有统计学意义（χ2=51.815，P=3.2796×10-4）。肿瘤组织中的 IL-37 与血清 AFP（χ2=5.515，P=0.048）和肝硬化（χ2=7.451，P=0.014）有关。PT 中 IL-37 的表达与性别（χ2=10.376，P=0.013）和肿瘤大小（χ2=8.118，P=0.04）有关。HCC 中 Oct4 的表达与患者的性别和肝硬化有关。重要的是，肿瘤组织中 IL-37 和 Oct4 之间存在负相关（r=-0.299，P=0.047），而在 PT 中则无相关性（P>0.05）。IL-37 使 HepG2 细胞中 Oct4 蛋白表达下调 63.35%（P<0.05），使 MHCC97H 细胞中 Oct4 蛋白表达下调 95.20%（P<0.05）。
肿瘤组织和 PT 中 IL-37 的表达与血清 AFP 和肝硬化、肿瘤大小有关。IL-37 蛋白表达与癌细胞系和肿瘤组织中的 Oct4 相关，但与 PT 不相关。本研究表明，IL-37 可能在 HCC 的发生发展中起作用。
