GRIM-19在肝细胞癌中的表达及与p-STAT3相关性的研究

Expression of GRIM-19 in Hepatocellular Carcinoma and Its Correlation with p-STAT3

目的:检测GRIM-19 mRNA、蛋白在肝细胞癌及非癌组织中的表达,探讨与p-STAT3的关系,及二者在肝细胞癌发生、发展中的作用。方法:免疫组化检测10例肝细胞癌及非癌组织中GRIM-19蛋白、p-STAT3蛋白的定位,RT-PCR和Western-blot检测40例肝细胞癌及非癌组织中GRIM-19mRNA和GRIM-19蛋白、p-STAT3蛋白表达。分析GRIM-19与临床病理特征的关系,及与p-STAT3的相关性。结果:在肝细胞癌及非癌组织中,GRIM-19、p-S TAT3分别定位于胞浆、胞核。GRIM-19mRNA在肝细胞癌的表达(0.40±0.31)低于非癌组织(0.56±0.67)(P<0.05),GRIM-19蛋白与mRNA表达一致。p-STAT3蛋白在肝细胞癌的表达(0.92±1.40)高于非癌组织(0.24±0.22)(P<0.05)。GRIM-19mRNA表达与临床分期、门脉癌栓有关,与性别、年龄、AFP、肿瘤大小、肝硬化、转移、组织分级无关,GRIM-19蛋白有同样的趋势。GRIM-19与p-STAT3负相关(r=-0.55,P<0.05)。结论:GRIM-19低表达可能与肝细胞癌发生、发展、侵袭等有关,并与p-STAT3共同促进肝细胞癌发生、发展。

Objective： To examine the expression of GRIM-19 mRNA and protein in hepatocellular carcinoma （ HCC ） tissue and homologous noncancerous liver tissue, to explore the correlation between GRIM-19 and p-STAT3 expression, and to analyze the functions of these proteins in the oncogenesis and progression of HCC. Methods： Immunohistochemistry was used to detect the cellular distribution of GRIM-19 and p-STAT3 proteins in 10 HCC and 10 noncancerous liver tissue samples. Reverse transcription-polymerase chain reaction （ RT-PCR ） and Western blot were used to determine the expression of GRIM-19 mRNA, GRIM-19 protein, and p-STAT3 protein in 40 specimens with HCC and corresponding noncancerous tissue of the liver. The relationship between GRIM-19 and various clinicopathologic features and the correlation between GRIM-19 and p-STAT3 were statistically analyzed. Results： In the HCC and noncancerous liver tissue, GRIM-19 protein was located in the cytoplasm, and P-STAT3 protein was located in the nuclei. The expression of GRIM-19 mRNA was significantly lower in HCC （ 0.40 ± 0.31 ） than in the corresponding noncancerous liver tissue （ 0.56 ± 0.67, P〈 0.05 ）, while the expression of GRIM-19 protein was consistent with the expression of GRIM-19 mRNA. By contrast, the expression of p-STAT3 protein was markedly higher in HCC （ 0.92 ± 1.40 ） than in the noncancerous liver tissue （ 0.24 ± 0.22, P〈 0.05 ）. The expression of GRIM-19 mRNA was correlated with the clinical stage and pylic tumor embolus, but not with gender, age, AFP, tumor size, liver cirrhosis, metastasis, or histologic grade. A similar trend was observed between these parameters and GRIM-19 protein expression. There was a negative correlation between the expression levels of GRIM-19 and p-STAT3 in HCC （ r = -0.55, P 〈 0.05 ）. Conclusion： Low erexpression of GRIM-19 in HCC may be associated with oncogenesis, progression, and invasion. Both GRIM-19 and p-STAT3 may promote the occurrence and development of liver tumors.