IQGAP2在肝细胞肝癌中的表达及其临床意义

Expression of IQGAP2 and its clinical significance in hepatocellular carcinoma

目的:认识肝细胞肝癌中含IQ模体的GTP酶活化蛋白2(IQ motif containing GTP aseactivating protein2,IQGAP2)的亚细胞定位和表达,及其在肝细胞肝癌(hepatocellular carcinoma,HCC中的作用.方法:分别通过Westernblot、免疫荧光和免疫组织化学染色分析IQGAP2在7种人肝癌细胞与正常肝细胞系中的表达、定位,及其在HCC组织样本中的表达与分布.结果:IQGAP2在Bel-7402、Bel-7404、SMMC-7721、SK-HEP-1、HLE和HL-7702等肝癌和正常成人肝细胞系中不表达,仅在HepG2和Hep3B等2种甲胎蛋白(AFP)表达阳性的人肝癌细胞系中表达.IQGAP2主要分布于细胞质,此外,在HepG2细胞中还具有明显的核膜和核仁定位.IQGAP2在HCC组织中表达降低(56.9%,29/51).其中,19例配对HCC组织的IQGAP2表达与肿瘤大小,AJCC分期和血清AFP水平相关(P=0.020,P=0.017,P=0.002);38例配对组织IQGAP2在肿瘤和癌旁正常肝组织中主要定位于胞质,部分细胞伴有胞核和胞膜定位.但是,IQGAP2的表达与肿瘤大小、分化程度、AJCC分期以及血清AFP表达水平无相关性.结论:IQGAP2蛋白可能参与细胞黏附、信号转导等过程,在肝癌的发生发展中发挥重要作用,是一种潜在的抑癌基因.

AIM： To investigate the expression of IQ motif containing GTPase activating protein 2 （IQGAP2） and its correlation with the clinicopathological parameters in hepatocellular carcinoma （HCC）, and to reveal the potential mechanisms of IQGAP2 underlying human hepatocarcinogenesis. METHODS： Western blot, immunofluorescence staining and immunohistochemical staining （IHC） were used to detect the expression and subcellular localization of IQGAP2 in 7 liver cancer and normal liver cell lines, as well as in 51 HCC tissue specimens. Meanwhile, the corresponding clinical data were analyzed retrospectively. RESULTS： Only two liver cancer cell lines, HepG2 and Hep3B, expressed IQGAP2 at the protein level. In addition, immunofluorescence results revealed that IQGAP2 was localized in cytoplasm and nuclei. Apparent nucleolus and karyotheca staining was observed in HepG2 cells. Furthermore, histological validation of clinical samples showed that IQGAP2 expression was significantly down-regulated in tumor tissues （56.9%, 29/51）. Meanwhile, the expression of IQGAP2 was associated with tumor size, AJCC staging and alpha-fetoprotein （AFP） expression level （P = 0.020; P = 0.017; P = 0.002）. The immunohistochemical staining results from 38 HCC specimens showed that IQGAP2 was mainly localized at cytoplasm in the tumor and adjacent normal liver cells. In addition, partial cells had cell membrane and nuclear localization. However, definite association was not observed between IQGAP2 levels and tumor size, histological degree, AJCC staging or AFP expression status. CONCLUSION： IQGAP2 expression is downregulated in tumor tissues of HCC cases, and IQGAP2 may be a potential marker and tumor suppressor gene involved in HCC. These novel findings may provide a basis for the determination of mechanism（s） underlying human hepatocarcinogenesis.