Expression Of Smad4 And P21 In Hepatocellular Carcinoma And Its Clinical Significance

Background and ObjectivePrimary hepatocellular carcinoma one of the most frequent tumors in our country is well known for its death rate,which seconds only to gastric carcinoma and esophageal carcinoma.The specific pathogenesy is not clear at present.Although a variety of antitumoral measures including surgery,irradiation and chemotherapy are taken,the 5-years survival rate of PHC is still low.To approach the pathogenesy and find new treatment is abnormally important.In this article we mainly approach HCC for which take possession of 90%in PHC.The carcinogenesis of HCC is progression with many steps and phases and its mechanism is rather complex.Modern molecular biology studies have shown that the occurrence and development of malignant tumors are associated with abnormal cell signal transduction,which is one of the important mechanisms of cancer formation,which will benefit to the therapies and prevention of HCC by studying the relations of the two.The abnormal of TGF-βsignaling pathway which was reported recently,plays an important role to induce emergence,development and metastasis of HCC.Smad4 gene known as DPC4(deleted in pancreatic cancer locus4,DPC4) plays a key role in TGF-βtransduction pathway.It acts as an anti-oncogene in a variety of tumors.The product of P21 gene is a cyclin-dependent kinase inhibitor protein,which can generally inhibit the action of phosphorylating kinase of CDK in G₁ stage and S stage. P21 the target gene of Smad4 may be involved in the regulation of cell proliferation and apoptosis functions in TGF-βsignaling system.Both of them make an effect on the development of tumors.To observe the expression of Smad4 and P21 in the tissue of HCC and adjacent normal tissue specimens and the relation-ship of them,we can approach an initial mechanism of the action of HCC.Materials and Methods60 surgically resected HCC tissues were collected.Among them male 39,female 21;aged 14-74 years,with an average age of(51±12.80);well-differentiated 13, moderate 38,poorly-differentiated 9;and there were 14 patients with metastasis. (including lymph node metastasis,in and out of the liver metastasis) All the patients had no chemotherapy and immunotherapy.Then took 20 adjacent normal tissue specimens as comparison.All the tissues were fixed in 10%neutral formalin and embedded in paraffin.The expression of Smad4 and p21 were detected by the PV two-way immunohistochemistry technique in HCC tissue and adjacent normal tissue, and the relationship of these results was analyzed.The data were analyzed by statistical software SPSS 13.0.x² test and spearman rank correlation were used to analyze the difference between different groups,a=0.05 was considered as the level of tests.Result1.The positive expression rate of smad4 was 33.7%in HCC tissue,and that was 80.0%in adjacent normal tissue,and there was significant difference between two groups(P＜0.05).2.The expression of smad4 had no correlated relationship with the age,sex,the diameter of the tumor and AFP content between the HCC tissue and the adjacent normal tissue(P＞0.05).The positive rates of smad4 expression were 92.3%,23.7% and 11.1%respectively in the high,moderate and poor differentiation group,and there was significant difference in the three groups(P＜0.05).There was significant difference of the positive expression rate of smad4 between the metastasis positive group(7.1%) and the metastasis negative group(45.70%)(P＜0.05). 3.The positive expression rate of p21 was 41.7%in HCC tissue,and was 70.0% in adjacent normal tissue,and there was significant difference between two groups (P＜0.05).4.The expression of p21 had no correlated relationship with the age,sex,the diameter of the tumor,stage of disease,metastasis and AFP content between the HCC tissue and the adjacent normal tissue(P＞0.05).5.In HCC tissue Smad4 protein expression was positively correlated with the expression of p21 protein(r=0.69,P＜0.01).Conclusions1.The low expression of Smad4 and p21 in HCC tissue were closely correlated with the occurrence and invasion of HCC.The tendency showed more poorly-differentiated the tissue lower expression the smad4 protein.2.Smad4 may be an early index for canceration of the hepatic cell and play an important role in early metastasis.3.Smad4 was positive significantly correlated with p21.Which suggests the two genes may stay at the same signaling pathway.Both regulate the invasion and metastasis of HCC.