The Relation Between The Expression Of RhoC And MMP-9 Protein And The Recurrence After Hepatectomy In The Patients With HCC

Objective: To describe the expression levels of RhoC and MMP-9 proteins and their relations with pathological characteristics and recurrence in primary hepatocellular carcinoma (HCC) , and investigate the role of RhoC and MMP-9 proteins in genesis, development, metastasis and recurrence after operation of HCC, including providing theoretical evidence for revealing invasion, metastasis and recurrence in HCC at molecular level, and objectively assess the diagnosis, therapeutic efficacy and prognosis of HCC.Methods: Liver specimens from 43 patients with HCC, 25 with hepatic cirrhosis and 23 with normal hepatic tissues were immunohistochemically stained for RhoC and MMP-9. The relationship between their expression and the pathological characteristics of HCC, as well as the relationship between the expression of RhoC and MMP-9 were analyzed. Their distinctions of expression in different pathologic tissues were studied. The multivariate COX proportional hazards model was used to analyze the prognostic recurrence risk factors.Results:1.RhoC protein was mainly expressed in the cytoplasm, the relationships between the expression and the clinical and pathological index were as followed: the expression of RhoC protein was not correlated with the gender, age, tumor size, satellite focus and the positive expression of alpha fetoprotein; but it was correlated with HBV infection, histological differentiation, integrity of liver capsule, invasion of portal vein, tumor stage (TNM) and lymphatic metastasis.2. MMP-9 protein was also mainly expressed in the cytoplasm. The relationships between the expression and the pathological index were as followed: the expression of MMP-9 protein was not correlated with the gender, age, tumor size, satellite focus HBV infection, and the positive expression of alpha fetoprotein; but it was correlated with histological differentiation, integrity of liver capsule, invasion of portal vein, tumor stage (TNM) and lymphatic metastasis.3. The expression level of RhoC in HCC tissues is higher than paraneoplastic ones, cirrhosis ones and normal ones. The expression of RhoC in paraneoplastic ones is higher than normal ones. But there is no significant statistical difference in the expression level of RhoC between paraneoplastic ones and cirrhosis ones, between cirrhosis ones and normal ones.4. The expression level of MMP-9 in the HCC tissues of patients with HCC is higher than paraneoplastic ones, cirrhosis ones and normal ones. But there is no significant statistical difference in the expression level of RhoC between paraneoplastic ones and cirrhosis ones, or between paraneoplastic tissues and normal ones, or between cirrhosis ones and normal ones.5.The expression level of RhoC is positively correlated with that of MMP-9 (rs'=0.495 P<0.01). 6.The median survival time was 46.00 months, while in the positive group it was 20.00 months, in the group of negative expression of RhoC. Respectively the median survival time was 49. 00 months, while in the positive group it was 25.00 months, in the group of negative expression of MMP-9. The median survival time was 56. 00 months, in the group of negative expression of both RhoC and MMP-9. It was 39. 00 months, in the group of negative expression of either RhoC or MMP-9. It was 19.00 months, in the group of positive expression of both RhoC and MMP-9.Conclusion:1.RhoC may play a role in the early stage and progression of HCC. The expression level of RhoC was positively correlated with the malignant degree.2. The expression level of MMP-9 was positively correlated with the malignant degree.3. The tumor-free survival time was negative related to the expression degree of RhoC and MMP-9 protein in the tumor tissues.4.The result of multivariate COX proportional hazards model showed that invasion of portal vein (including micrometastasis ), lymph node metastasis, resection margin less than 2cm, size bigger than 3cm , poorly histological differentiation, positive expression of RhoC and MMP-9 were the independent risk factors of recurrence after operation of HCC.5. The abnormal overexpression of RhoC protein and MMP-9 protein may indicate a higher malignant behavior and a higher rate of recurrence after operation, which may be clinical guidingsignificance for chemoprophylaxis.