Abstract:
Objective To investigate the relationship between inhibitor of growth 4(ING4) expression and recurrence/metastasis and prognosis of liver transplantation for hepatocellular carcinoma(HCC).
Methods Thirty HCC patients who underwent liver transplantation in the Liver Transplantation Center of Jiangxi Province People's Hospital from May 2003 to December 2007, were selected as objects. Tissue samples were acquired from HCC tissue and pericarcinomatous liver tissue(PCLT, 1 cm beside HCC tissue), which were resected by operation. Expression of ING4 protein in HCC tissue and PCLT was quantitatively measured by immunohistochemistry. Positive expression ratio and expression intensity of ING4 were compared between HCC tissue and PCLT. The expression level of ING4 in the tissues was detected by Western blot. According to the results of Western blot, ratio of ING4 expression between HCC tissue and PCLT was calculated. As ratio of 0.48 was boundary, 30 patients were divided into ING4 low expression group(n=15)and ING4 high expression group(n=15). Clinical pathological characteristics, recurrence/metastasis and prognosis of liver transplantation for hepatocellular carcinoma were analyzed between two groups.
Results The immunohistochemistry result showed that the positive expression ratio of ING4 was respectively 63%(19/30)in HCC tissue and 93%(28/30)in PCLT, and there was significant difference(P<0.05). The strong positive expression ratio was 27%(8/30)in HCC tissue and 63%(19/30)in PCLT,and there was significant difference(P<0.05). The Western blot result showed that positive expression ratio of ING4 was 70%(21/30) in HCC and 97%(29/30)in PCLT,and there was significant difference(P<0.05). The expression level of ING4 protein in PCLT was higher than that in HCC tissue(197±31 vs. 109±24,P<0.05). In 30 pairs of samples, the ratio of ING4 protein down-regulation in HCC tissue was 83%(25/30). In clinical pathological characteristics, there were significant differences in number of tumor nodes(P=0.025), vein invasion(P=0.035), extrahepatic metastasis(P=0.017)and tumor cell differentiation(P=0.025) between ING4 low expression group and ING4 high expression group. Accumulative recurrence/metastasis rate of ING4 high expression group was lower than that of ING4 low expression group, and survival rate of ING4 high expression group was higher than that of ING4 low expression group(both in P<0.05). Median survival time of ING4 high expression group was longer than that of ING4 low expression group(720 d vs. 540 d, P<0.05).
Conclusions The expression level of ING4 protein decreases in HCC tissue. The decrease is related with recurrence/metastasis after liver transplantation for HCC and affects the prognosis of patients.