The Expressions And Correlations Of Smac, Survivin And Caspase-3 In Hepatocellular Carcinoma

Background and ObjectivePrimarily hepatocellular carcinoma(HCC) is a seriously malignant tumor with very poor prognosis,called"the king of cancer".Half of the hepatoma patients are in China,and liver cancer occupies the secound position among the case fatality of malignant tumor.At present,there are many problems in the diagnosis and treatment of liver cancer,such as difficultly early diagnosis,high recurrence and metastasis,directly treatment,loss of original new drugs and few therapeutic tools,which require combination of fundamental and clinical research.Prevention in advance,early diagnosis,treatment personality,combined therapy,also prevent and cure the metastasis and recurrence,whitch will raise the level of diagnosing and treating liver cancer versatilitily and multistrataly if all these come true.Apoptosis is a proeess of cell death that actively induces a suicide process under the control of a series of gene regulators, the final result of loss of reaction ability of spontaneous apoptosis is related to the occurrence and development of cancer.Smac(second mitochondria-derived activator of caspase) is a new mitochondria-derived protein and a regulatory factor of apoptosis in cytoplasmic released by mitochondria.Smac can combine with many IAPs(Inhibitor of apoptosis proteins) molecules,and it is only one protein discoveried in mammalian cell directly repress IAPs,which will make IAPs lost the ability to inhibit the activity of Caspase.Smac promotes the course of apoptosis,and the low expression of Smac in tumor tissue maybe related with the occurrence and development of tumor.IAPs family is discovered as a major anti-apoptosis family recently.Survivin is one of the IAPs family with the smallest molecular weight and most highly effect for anti-apoptosis.Survivin can inhibit apoptosis through combinding with Caspase-3 and Caspase-7 and suppressing their activity.Caspase-3 is a proteolytic enzyme which mediates apoptotis.That is an important effective enzyme of caspase family,which is a effector molecule performed apoptosis.As the capital performor of apoptosis,the relationship between Caspase-3 and tumor is a hot spot being studied and researched by scholar in the world.Through determining the activity of caspase-3,we can get the message of tumors' occurrence and development,and offer some advantageous help for tumors' diagnosis and target gene therapy.At present,the pathogenesy of hepatocelluar carcinoma is still not quite clear.This experiment applies the immunohistochemistry method to detect the expression of Smac,Survivin and Caspase-3 in hepatocelluar carcinoma tissue and normal liver tissue,and analyze the relationship among them and with the clinical-patho-characteristic of hepatocelluar carcinoma,which is aim to approach the occurrence and development of primary hepatocelluar carcinoma and to explore a new method for early diagnosis,treatment and prognosis of hepatocelluar carcinoma.Materials and Methods50 cases of hepatocelluar carcinoma samples were collected in the pathology department of the first affiliated hospital of ZhengZhou university,which were resected from January in 2004 to December in 2007 and identified by pathological detection,which is the experiment group.In addition,15 cases of normal liver tissue resected from Liver surgical trauma are collected as the control group.Prepare the collected samples with routine method.We carry out histochemical stain with immunohistochemistry method(PV-9000,two step method).The software package SPSS13.0 was used to data processing.The analysis of all data was performed with x~2 test or Fihser's exact probability test,and Spearman rank correlation withα=0.05 as statistically significant value.Results1.the expression of Smac in the different hepatic tissuesOf the 50 cases of HCC tissues,there were 23 cases shown positive expression, and the positive expression rate was 46.0%.All of the normal hepatic tissues shown positive expression,that is the positive expression rate was 100%.There was statistical significance for the positive expression of Smac between HCC tissues and normal hepatic tissues(P＜0.05).The positive expression of Smac was not correlated with HCC patient's age,gender,HbsAg,AFP value,hepatic function,histological stage,number of tumor,diameter of tumor and portal vein carcinomatous epistomium(P＞0.05).There were 34 cases withⅠ～Ⅱstage and 16 cases withⅢstage divided into groups by clinical stage.Of the 34 cases ofⅠ～Ⅱstage,there were 19 cases shown positive expression,and the positive expression rate was 55.9%;Of the 16 cases ofⅢstage,there were 4 cases shown positive expression,and the positive expression rate was 25.0%.There was statistical significance for the positive expression of Smac between the two groups(P＜0.05).The positive expression of Smac was correlated with HCC patient's clinical stage.In other words,the higher the clinical stage of hepatocelluar carcinoma is,the lower the positive expression rate of Smac is.2.the expression of Survivin in the different hepatic tissuesOf the 50 cases of HCC tissues,there were 34 cases shown positive expression, and the positive expression rate was 68.0%.All of the normal hepatic tissues shown negative expression.There was statistical significance for the positive expression of Survivin between HCC tissues and normal hepatic tissues(P＜0.05).The positive expression of Survivin was correlated with HCC patient's histological stage and diameter of tumor.There were 33 cases withⅠ～Ⅱstage and 17 cases withⅢ～Ⅳstage divided into groups according to Edmondson's method for histological stage.Of the 33 cases ofⅠ～Ⅱstage,there were 19 cases shown positive expression,and the positive expression rate was 57.6%,Of the 17 cases ofⅢ～Ⅳstage,there were 15 cases shown positive expression,and the positive expression rate was 88.2%.There was statistical significance for the positive expression of Survivin between the two groups(P＜0.05).Divided into groups according to the diameter of tumor,there were 36 cases of =5cm and 14 cases of＞5cm,and there were 21 cases of =5cm group and 13 cases of＞5cm group shown positive expression of Survivin with the positive expression rate 58.3%and 93.9%.There was statistical significance for the positive expression of Survivin between the two groups(P＜0.05).The positive expression of Survivin was not correlated with HCC patient's age,gender,HbsAg,AFP value,hepatic function,clinical stage,number of tumor and portal vein carcinomatous epistomium (P＞0.05).3.the expression of Caspase-3 in the different hepatic tissuesOf the 50 cases of HCC tissues,there were 24 cases shown positive expression, and the positive expression rate was 48.0%.Of the 15 cases of normal hepatic tissues, there were 13 cases shown positive expression,and the positive expression rate was 86.7%.There was statistical significance for the positive expression of Caspase-3 between HCC tissues and normal hepatic tissues(P＜0.05).The positive expression of Caspase-3 was correlated with HCC patient's histological stage.There were 33 cases withⅠ～Ⅱstage and 17 cases withⅢstage divided into groups according to Edmondson's method for histological stage.Of the 33 cases ofⅠ～Ⅱstage,there were 21 cases shown positive expression,and the positive expression rate was 63.6%;Of the 17 cases ofⅢstage,there were 3 cases shown positive expression,and the positive expression rate was 17.6%.There was statistical significance for the positive expression of Caspase-3 between the two groups(P＜0.05).The positive expression of Caspase-3 was not correlated with HCC patient's age,gender,HbsAg,AFP value, hepatic function,clinical stage,number of tumor,diameter of tumor and portal vein carcinomatous epistomium(P＞0.05).4.The correlations of the expressions among Smac,Survivin and Caspase-3 in hepatocellular carcinomaThere was a negative correlation between the expression of Smac and Survivin in hepatocellular carcinoma(r=-0.485,P＜0.05);There was a positive correlation between the expression of Smac and Caspase-3 in hepatocellular carcinoma(r=-0.318, P＜0.05);There was a negative correlation between the expression of Survivin and Caspase-3 in hepatocellular carcinoma(r=-2.059,P＜0.05).Conclusion1.Smac and Caspase-3 may co-participate in the regulational course of hepatic apoptosis,the down regulation of Smac and Caspase-3 and the up-regulation of Survivin may promote the occurrence and the development course of hepatocelluar carcinoma.2.There was positive feedback or negative feedback mechanism among Smac,Survivin and Caspase-3 perhapsly.Accordingly to affect apoptosis of hepatoceUular carcinoma, so promote or refrain aggravation and succession of tumor.To detect Smac,Survivin and Caspase-3 together may contribute to therapy and prognosis judgment of hepatocellular carcinoma.