Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
Department of Oncology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi, China.
Cytokine. 2019 Jun;118:124-129. doi: 10.1016/j.cyto.2018.03.036. Epub 2018 Apr 12.
Interleukin (IL)-33/ST2 pathway plays a pivotal role in tumorigenesis through influencing cancer stemness, tumor growth, metastasis, angiogenesis, and accumulation of regulatory T cells in tumor microenvironments. The aim of this study was to investigate the association of IL-33 rs7025417 and ST2 rs3821204 with the risk of hepatocellular carcinoma (HCC). Genotyping of IL-33 rs7025417 and ST2 rs3821204 was carried out using a Taqman assay. IL-33 and ST2 mRNA was examined using real-time PCR and plasma IL-33 and sST2 levels were measured using enzyme-linked immunosorbent assay. The ST2 rs3821204 CC genotype was associated with a significantly increased risk of HCC (CC vs. GG: adjusted OR = 2.29, 95% CI, 1.39-3.78; dominant model: adjusted OR = 1.58, 95% CI, 1.12-2.23; recessive model: adjusted OR = 1.88, 95% CI, 1.21-2.93; C vs. G: adjusted OR = 1.53, 95% CI, 1.20-1.95). Gene-environment interaction analysis showed that the risk effect of rs3821204 CG/CC genotypes was more evident in smokers (adjusted OR = 1.70, 95% CI, 1.13-2.55) and drinkers (adjusted OR = 1.57, 95% CI, 1.04-2.37). The increased risk was also observed in combined analysis. Moreover, HCC patients with ST2 rs3821204 CC genotype had higher levels of mRNA and protein expression (P < 0.05). These findings suggest that ST2 rs3821204 CC genotype may contribute to hepatocarcinogenesis by enhancing ST2 production at the transcriptional and translational level.
白细胞介素 (IL)-33/ST2 通路通过影响肿瘤干细胞特性、肿瘤生长、转移、血管生成和肿瘤微环境中调节性 T 细胞的积累在肿瘤发生中起着关键作用。本研究旨在探讨 IL-33 rs7025417 和 ST2 rs3821204 与肝细胞癌 (HCC) 风险的关联。采用 Taqman assay 检测 IL-33 rs7025417 和 ST2 rs3821204 的基因分型。使用实时 PCR 检测 IL-33 和 ST2 mRNA，使用酶联免疫吸附试验测量血浆 IL-33 和 sST2 水平。ST2 rs3821204 CC 基因型与 HCC 的风险显著增加相关（CC 与 GG：调整后的 OR=2.29，95%CI，1.39-3.78；显性模型：调整后的 OR=1.58，95%CI，1.12-2.23；隐性模型：调整后的 OR=1.88，95%CI，1.21-2.93；C 与 G：调整后的 OR=1.53，95%CI，1.20-1.95）。基因-环境交互作用分析表明，rs3821204 CG/CC 基因型的风险效应在吸烟者（调整后的 OR=1.70，95%CI，1.13-2.55）和饮酒者（调整后的 OR=1.57，95%CI，1.04-2.37）中更为明显。联合分析也观察到了这种增加的风险。此外，ST2 rs3821204 CC 基因型的 HCC 患者具有更高水平的 mRNA 和蛋白表达（P<0.05）。这些发现表明，ST2 rs3821204 CC 基因型可能通过增强转录和翻译水平的 ST2 产生促进肝癌发生。
