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目的:探讨RhoGDI2和CIAPIN1在肝癌组织中的表达情况及临床病理意义。方法:选取2013年5月~2015年9月在我院接受治疗的肝癌患者112例,应用免疫组化法检测112例肝癌组织标本、癌旁正常肝组织标本中RhoGDI2和CIAPIN1两种蛋白的表达情况,并分析两种蛋白的表达与肝癌增殖侵袭的相关性。从GEO datasets数据库中搜索出与肝癌增殖侵袭相关的基因数据,使用GEO2R分析肝癌组织中与RhoGDI2或CIAPIN1表达一致或相反的基因数据,最后应用DAVID对这些基因进行基因信号通路富集,找到RhoGDI2和CIAPIN1调控肝癌增殖侵袭的可能作用机制。结果:肝癌组织中,RhoGDI2和CIAPIN1表达阳性率分别为66.96%、27.68%,RhoGDI2的表达与淋巴结转移和远处转移密切相关,与患者的年龄、性别、原发灶分期、原发灶直径、组织学分级及TNM分期等均无相关性,而CIAPIN1在肝癌中的表达与患者年龄、性别、原发灶分期、原发灶直径、淋巴结转移及远处转移并无密切相关性,仅与组织学分级、TNM分期密切相关,其中RhoGDI2的表达与癌细胞转移呈正相关,而CIAPIN1的表达与肝癌组织学分级呈负相关,与TNM分级呈正相关。通过基因信号通路富集分析显示肝癌组织中RhoGDI2可能是通过PI3K-Akt-mTOR和Rho-ROCK信号通路介导肝癌细胞的增殖侵袭,而CIAPIN1可能是通过调控ERK1/2-MAPK通路影响肝癌增殖侵袭。结论:RhoGDI2和CIAPIN1在肝癌组织中均呈高表达,RhoGDI2的高表达可能会促进肝癌细胞的淋巴及远处转移,而CIAPIN1与肝癌细胞转移无关,与肝癌发生的严重状况密切相关。二者可能是通过不同的信号通路共同介导肝癌细胞的分化、转移等。
Objective: To investigate the expression of RhoGDI2 and CIAPIN1 in hepatocellular carcinoma and its clinicopathological significance. Methods: From May 2013 to September 2015 in our hospital, 112 patients with hepatocellular carcinoma who were treated in our hospital were selected. The expression of RhoGDI2 and CIAPIN1 proteins in 112 specimens of HCC tissues and adjacent normal liver tissues were detected by immunohistochemistry And analyzed the correlation between the expression of two proteins and the invasion and proliferation of hepatocellular carcinoma. We searched GEO datasets database for the gene data related to the proliferation and invasion of hepatocellular carcinoma, analyzed the gene data consistent with or opposite to the expression of RhoGDI2 or CIAPIN1 in liver cancer tissue by GEO2R, and finally enriched the gene signal through these genes using DAVID, and found RhoGDI2 and CIAPIN1 regulates the possible mechanism of hepatocellular carcinoma invasion and proliferation. Results: The positive rates of RhoGDI2 and CIAPIN1 in hepatocellular carcinoma were 66.96% and 27.68%, respectively. The expression of RhoGDI2 was closely related to the lymph node metastasis and distant metastasis. The positive rates of RhoGDI2 and CIAPIN1 were closely related to the age, sex, staging, Histological grade and TNM staging, etc. There was no correlation between the expression of CIAPIN1 and the age, sex, staging of primary tumor, diameter of primary tumor, lymph node metastasis and distant metastasis in HCC, Grade and TNM stage. The expression of RhoGDI2 was positively correlated with the metastasis of cancer cells, while the expression of CIAPIN1 was negatively correlated with the histological grade of HCC and positively correlated with the grade of TNM. Enrichment analysis of gene signal pathways showed that RhoGDI2 may be involved in the proliferation and invasion of hepatocellular carcinoma cells through PI3K-Akt-mTOR and Rho-ROCK signaling pathways, while CIAPIN1 may affect the proliferation and invasion of hepatocellular carcinoma through the regulation of ERK1 / 2-MAPK pathway . Conclusions: RhoGDI2 and CIAPIN1 are all highly expressed in HCC. High expression of RhoGDI2 may promote lymphatic and distant metastasis of hepatocellular carcinoma cells. However, CIAPIN1 is not related to the metastasis of HCC, which is closely related to the severity of HCC. Both may be mediated through different signaling pathways of liver cancer cell differentiation, metastasis and so on.