The Study Of The Relationship Between The Expression Of ZHX2 Gene And Metastasis In Hepatocellular Carcinoma

Objective: To study the expression of zinc-fingers and homeoboxes 2(ZHX2) in hepatocellular carcinoma(HCC),and to explore the relationship between the expression of ZHX2 gene and the metastasis of HCC. Methods:(1)RT-PCR and immunohistochemical(IHC) were performed to detect the ZHX2 mRNA and protein of 35 HCC tumor tissues and adjacent-tumor liver tissues and 8 cases of normal liver tissues. The results were analyzed by combination with the clinical and pathological data of the patients.(2)Tissue microarray and immunohistochemical technique were performed to detect the ZHX2 protein,matrix metalloproteinase 9 protein,tissue inhibitor of matrix metalloproteinase 1 protein of 136 HCC tumor tissues and adjacent-tumor liver tissues,57 cases of normal liver tissues. Results:(1) 11 cases with preoperative metastasis and 24 cases without metastasis in 35 HCC. The positive rate of the ZHX2 mRNA and protein on tumor tissues, adjacent-tumor liver tissues and normal liver tissues are: 37.1%(13/35),62.9%(22/35),87.5%(7/8) and 25.7%(9/35),54.3%(19/35),75%(6/8),The positive rate of ZHX2 mRNA and protein on tumor tissues lower than adjacent-tumor liver tissues and normal liver tissues(P<0.05). The positive rate of ZHX2 mRNA and protein in cases with preoperative metastasis and 24 cases without metastasis are: 9.1%(1/11)and27.3%(3/11),lower than cases of without metastasis(P<0.05).(2) expression of ZHX2 mRNA was correlated with the serum lever of AFP(P<0.05), was not correlated with age, sex, serum of HBsAg, tumor size, differentiation grade,liver cirrhosis.(3)136 cases of HCC, On tumor tissues, adjacent-tumor liver tissues,normal liver tissues, the positive rate of the ZHX2 protein are 22.8%,36.8%,38.6%;the positive rate of the MMP-9 protein are 72.1%,52.9%,50.9%;the positive rate of the TIMP-1 protein are 67.6%,79.4%,82.5%. The positive rate of ZHX2 and TIMP-1 on tumor tissues lower than adjacent-tumor liver tissues and normal liver tissues(P<0.05), The positive rate of MMP-9 on tumor tissues higher than adjacent-tumor liver tissues and normal liver tissues(P<0.05).(4)136 cases of HCC , 54 cases with preoperative metastsis,82 cases without metastasis. On Cases with preoperative metastasis and without metastasis , the positive rate of ZHX2 protein are 13% and 29.3%; the positive rate of MMP-9 protein are 85.2% and 63.4%; the positive rate of TIMP-1 protein are 57.4% and 74.4%.The positive rate of ZHX2 and TIMP-1 on cases with preoperative metastasis lower than cases of without metastasis(P<0.05), The positive rate of MMP-9 on cases with preoperative metastasis higher than cases of without metastasis(P<0.05).(5) 136 cases of HCC, the expression rate of MMP-9 was higher in the ZHX2-positive subgroup(P<0.05). Conclusion: (1) Low expression of ZHX2 might be break the balance of the expression of TIMP-1 and MMP-9, promoted the metastasis of HCC. (2) Low expression of ZHX2 activated the expression of AFP.