肝细胞癌中IL-33/ST2的表达与巨噬细胞浸润的相关性研究  

Correlation between IL-33/ST2 expression and macrophage infiltration in hepatocellular carcinoma

作　　者：依力哈木·买买提[1] 钟锴 郭强[1] 肖开提·阿不都哈德尔[1] Yilihamu Maimaiti;ZHONG Kai;GUO Qiang;Xiaokaiti Abuduhadeer(Intra-Day Ward,Department of Outpatient,Medical Affairs,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院医务部门诊部日间病房,乌鲁木齐830054

出　　处：《新疆医科大学学报》2022年第11期1248-1255,共8页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金(2018D01C220)。

摘　　要：目的探讨白介素-33(interleukin-33,IL-33)和肿瘤发生抑制蛋白2(suppression of tumorigenicity 2,ST2)在肝细胞癌中的表达与巨噬细胞浸润的相关性。方法选取30例肝细胞癌患者的癌组织和远端肝组织,通过苏木精-伊红(hematoxylin-eosin,HE)染色观察其病理变化,免疫组织化学染色和实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)法检测巨噬细胞标志物CD68、M1型巨噬细胞标志物S100A9、M2型巨噬细胞标志物CD163、IL-33及ST2在肝细胞癌组织中的表达情况;分析IL-33、ST2与M1、M2型巨噬细胞标志物S100A9、CD163在肝细胞癌组织中表达的相关性及CD68、CD163、S100A9、IL-33、ST2在肝细胞癌组织的表达与临床指标之间的相关性。结果在肝细胞癌组织中可见核大而不规则的癌细胞,呈多角形排列成巢状,索间有丰富的血窦,核仁明显。在30例肝细胞癌患者中高、中分化22例(73.33%),低分化8例(26.67%),伴有淋巴结转移4例(13.33%)。免疫组织化学染色结果显示,CD68、CD163、S100A9、IL-33及ST2阳性细胞主要在肝细胞癌组织中高表达,远端肝组织中仅有少量表达,差异有统计学意义(P<0.01)。qRT-PCR结果显示,在肝细胞癌组织中CD68、CD163、S100A9、IL-33及ST2 mRNA的相对表达量较远端肝组织明显增加,差异有统计学意义(P<0.01)。肝细胞癌组织中巨噬细胞主要以CD163阳性M2型巨噬细胞为主,并与IL-33、ST2在肝细胞癌组织中的表达均呈正相关(P<0.01);M1型巨噬细胞标志物S100A9的表达与IL-33、ST2在肝细胞癌组织中的表达无相关性(P>0.05)。上述指标在肝细胞癌组织的表达与临床指标之间相关性系数分析发现,M2型巨噬细胞标志物CD163的表达与分化程度呈正相关(P<0.05)。结论IL-33/ST2可能参与肝细胞癌组织中巨噬细胞向M2型巨噬细胞极化的过程。Objective To study the relation of interleukin-33(IL-33)/suppression of tumorigenicity 2(ST2)expression and macrophage infiltration in hepatocellular carcinoma.Methods Cancer and distant liver tissues were collect-ed from 30 patients with hepatocellular carcinoma.Pathological changes were observed through hematoxylin-eosin(HE)staining.Expression of macrophage marker CD68,M1-type macrophage marker S100A9,M2-type macrophage marker CD163,IL-33 and ST2 in hepatocellular carcinoma tissues were detected through immunohistochemistry and quantitative real time polymerase chain reaction(qRT-PCR)analysis.Correlation between IL-33,ST2 and M1-,M2-type macrophage marker S100A9,CD163 expression in hepatocellular carcinoma tissues were analyzed through correlation coefficient analysis,which were also used to analyse the relation between the expression of CD68,CD163,S100A9,IL-33,ST2 in hepatocellular carcinoma tissues and clinical indicators.Results There were cancer cells with large nucleus and irregular shape in hepatocellular carcinoma tissues,which were polygonal and arranged into a nest with abundant blood sinuses between the cords and obvious nucleoli.Among 30 patients with hepatocellular carcinoma,22 cases(73.33%)had high to medium differentiation,8 cases(26.67%)had low differentiation,and 4 cases(13.33%)had lymph node metastasis.Immunohistochemical results showed that CD68,CD163,S100A9,IL-33 and ST2 positive cells expressed at high levels in hepatocellular carcinoma tissues,whose expression were at low levels in distant liver tissues,and the differences were statistically significant(P<0.01).qRT-PCR analysis demonstrated that expression levels of CD68,CD163,S100A9,IL-33 and ST2 mRNA in hepatocellular carcinoma tissues were significantly higher than those in distant liver tissues,and the differences were statistically significant(P<0.01).Macrophages in hepatocellular carcinoma tissues were mainly CD163 positive M2-type macrophages,whose expression were positively correlated with IL-33 and ST2 expression in hepatocellular

关 键 词：肝细胞癌 巨噬细胞 白介素-33 肿瘤发生抑制蛋白2 

分 类 号：R735[医药卫生—肿瘤]