Expression Of GRIM-19 And STAT3 In Hepatocellular Carcinoma Tissues And Its Significance

Background Hepatocellular carcinoma(HCC)is the major primary malignant tumor in the human liver. But the molecular changes leading to liver cell transformation remain largely unknown. In recent years, studies have shown that the occurrence of the HCC with certain oncogene activation and inactivation of tumor suppressor gene has a certain relationship. Made from the gene level of prevention and treatment of HCC theory ,which has provided new vision for the treatment of HCC. Gene associated with retinoid-IFN-induced mortality-19 (GRIM-19) is one of the death-related genes induced by retinoid-interferon screened by Angell et al. It is a 16KD protein constituted by 144 amino acids, which is located at 19p13.1 of human chromosome. It can specifically bind to STAT3 to block intracellular STAT3 entering nucleolus and inhibit the expression of STAT3 gene and cell grown through down-regulating its transcription activity. During viral oncogenesis,GRIM-19 may be a general target protein similar to other cellular tumor suppressors, and it can in tract with NOD2 and GW112.Its over-expression could suppress proliferation and promote apoptosis of tumor cells grown, over-expression of GRIM-19 enhances the sensitivity of cells to IFN-RA-induced death. Research has confirmed that GRIM-19 was concerned with human renal cell carcinomas,urinary system tumor,lung cancer and many other malignancies, and the GRIM-19 protein was sever decrease or deletion in renal cell carcinomas and neoplasms. Other researches found that the mRNA and protein level of GRIM-19 gene in colorectal cancer tissue,lung cancer tissue,cervical cancer cell and ovary carcinoma cell was significantly lower than that in normal tissue and normal cell. However, the expression of GRIM-19 and STAT3 in HCC had never been reported. Objective This study was to investigate the expression of GRIM-19 and STAT3 in hepatocellular carcinoma,the corresponding adjacent normal liver tissues,liver cirrhosis tissues and normal liver tissues, and compare the expression lever of them. To explore the correlations with pathological grade,AFP and portal vein tumor thrombus.Methods The expression of GRIM-19 and STAT3 in 31 hepatocellular carcinoma,the corresponding adjacent normal liver tissues,20 liver cirrhosis tissues and 10 normal liver tissues was examined by SP immunohistochemistry staining.Results 1.Immunohistochemistry results showed that the positive rate of GRIM-19 protein in HCC was 51.5% ( 23/52 ) ,not significantly between HCC and the corresponding adjacent normal liver tissues64.5% (20/31) (p>0.05),but the positive rate of GRIM-19 protein in HCC was significantly lower than 84.6%(22/26)in hepatic cirrhosis tissues(p<0.05), and the expression rate of GRIM-19 protein in normal liver tissues specimen was 40.0%(4/10), significantly lower than that in hepatic cirrhosis tissues(p<0.05).2.Immunohistochemistry results showed that the positive rate of STAT3 protein in HCC was 67.7%(21/31), 41.9%(13/31)in the corresponding adjacent normal liver tissues, 35.0%(7/20)in hepatic cirrhosis tissues, and the expression rate of STAT3 protein in normal liver tissues specimen was 20.0%(2/10).The positive rate of STAT3 protein in HCC was significantly higher than the corresponding adjacent normal liver tissues,hepatic cirrhosis tissues and normal liver tissues(p<0.05),and the expression rate of STAT3 protein were not significantly among hepatic cirrhosis tissues,the corresponding adjacent normal liver tissues and normal liver tissues (p>0.05).3.Expression of GRIM-19 was related to differentiation degree of the hepatocellular carcinoma (P<0.05) , the relative amount of GRIM-19 proteins expression of high differentiation degree of the hepatocellular carcinoma were significantly higher than those of low differentiation degree of the hepatocellular carcinoma. There was no correlation of protein expression of GRIM-19 with patient's gender,age,the stage of cancer,HBsAg,AFP and portal vein invasion. But there was no correlation of protein expression of GRIM-19 with patient's gender,age,the stage of cancer,HBsAg,AFP,differentiation degree of the hepatocellular carcinoma and portal vein invasion.4.GRIM-19 expression in hepatocellular carcinoma was negatively correlated to STAT3 expression (r=-0.468,p<0.05).Conclusions The high expression of STAT3 and the low expression of GRIM-19 co-exist in hepatocellular carcinoma, GRIM-19 may participate in the tumorigenesis and development of hepatocellular carcinoma and hepatic cirrhosis, and GRIM-19 may be as a new tumor marker to hepatocellular carcinoma early screening.