RhoGDI2和CIAPIN1在肝癌组织中的表达及其临床病理意义

Expressions and Clinicopathological Significances of RhoGDI2 and CIAPIN1 in the Liver Cancer

目的：探讨RhoGDl2和CIAPINl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RhoGDl2和CIAPINl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GEOdatasets数据库中搜索出与肝癌增殖侵袭相关的基因数据，使用GE02R分析肝癌组织中与RhoGDl2或CIAPINl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RhoGDl2和CIAPlNl调控肝癌增殖侵袭的可能作用机制。结果：肝癌组织中，RhoGDl2和CIAPINl表达阳性率分别为66．96％、27．68％，RhoGDl2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CIAPINl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RhoGDl2的表达与癌细胞转移呈正相关，而CIAPINl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RhoGDl2可能是通过P13K—Akt—mTOR和Rho—ROCK信号通路介导肝癌细胞的增殖侵袭，而CIAPINl可能是通过调控ERKl／2．MAPK通路影响肝癌增殖侵袭。结论：对mGDl2和CIAPINl在肝癌组织中均呈高表达，RhoGDl2的高表达可能会促进肝癌细胞的淋巴及远处转移，而CIAPINl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 expressions and clinicopathological significances of RHOGDI2 and CIAPIN1 in the liver cancer. Methods： 112 cases of patients with liver cancer admitted in our hospital from May 2013 to September 2015 were chosen for the research, and the expressions of RhoGDI2 and CIAPIN 1 in the samples of liver cancer and the surrounding normal tissues were detected by immunohistochemistry and the impact of both genes on the proliferation and invasion of liver cancer were analyzed. The relative genes related to the proliferation and invasion from GEO datasets were researched; the genes that expressed the same trend or the opposite trend with RhoGDI2 or CIAPIN1 with GEO2R, online DAVID tools were used for mapping differentially expressed genes to signaling pathway, and finding the possible mechanisms that RhoGDI2 and CIAPIN1 worked on the proliferation and invasion of liver cancer. Results： The positive expression rates of RhoGDI2 and CIAPIN1 in liver cancer were 66.96 %, 27.68 % respectively. And the expression of both genes had a close contact with the process of liver cancer, and RhoGDI2 had a positive correlation with the lymphatic metastasis and distant metastasis of liver cancer and there was no relationship with age, gender, primary tumors in installment, primary focal diameter, histologic classification, TNM Installment. However, the expression of CIAPIN1 had no relationship with age, gender, primary tumors in installment, primary focal diameter, lymphatic metastasis and distant metastasis. But its expression had relationship with histologic classification and TNM installment. The expression of RhoGDI2 had positive relationship with metastasis of liver cancer, the expression of CIAPIN1 had positive relationship with histologic classification and negative relationship with TNM installment. And RhoGDI2 appeared to influence the PI3K-Akt-mTOR and Rho-ROCK pathway to play parts in regulating the proliferation and invasion of liver cancer with the help of DAVID tools, while CIAPIN1 may impact the process through ERK1/2-MAPK signaling pathway. Conclusions： Both RhoGDI2 and CIAPIN1 were highly expression in the liver cancer, and the high expression of RhoGDI2 might promote the invasion of liver cancer, and the expression of CIAPIN1 had no relationship with the invasion situation, but had a positiverelationship with the severity of liver cancer, the two genes might play a role in the invasion and differentiation of liver cancer via different signaling pathway.