| Research BackgroundThe primary liver cancer(PLC) is one of the most common malignant tumors all over the world.There are620,000people died annually because PLC,according to the annual human health report released by WHO. The pathological types of PLC include the hepatocellular carcinoma (HCC),the cholangiocellular carcinoma and the mixed type carcinoma.HCC is the most common pathological type.The proportion of HCC in total liver cancer patients reached90%.,and the patients with HCC are often connected with hepatocirrhosis.Today the measures to treat HCC include surgery,TACE,RFA,MWA,PEI,HIF U, radiation and chemotherapy, biological immune therapy method,liver transplantation and so on. Although many new technologies are used to make the comprehensive treatment of HCC a huge improvement, but the rate of transfer recurrence or death of patients with HCC has not been improved fundam-entally. According to Japanese statistics,among the patients who accepted the liver resections,the5-year survival rate is from30%to60%. For the patients with small HCC, the5-year survival rate is from50%to60%. For the patients with big HCC, the 5-year survival rate is from20%to30%.Among th patients who accepted the palliative treatment, the5-year survival rate is much lower. For example, the5-year survival rate of the patients who accepted TACE is from7%to10%.Liver transplantation is not a goog treatment for all the HCC patients. For the patients who accepted liver transplantation with a single nodule smaller than4cm in diameter, the5-year survival rate is57%. For the patients who accepted liver transplantation with a single nodule bigger than8cm in diameter, the5-year survival rate is ongly11%.The prognosis of HCC patients who accepted a comprehensive treatment would be improved.The long-term healing effect of HCC is not satisfactory mainly due to cancer recurrence. The follow-up statistics showed that the cancer recurrence rates reached14,3％within one year after surgery resection,35.7%within two years,42.9%within three years.We are still not clear about the mechanism of malignant tumor recurrence and metastasis.In order to better treating HCC, many scholars studied the biology microbehavior, based on molecular biology. They have found that abnormal expressions of cell surface proteins,for example,cell adhesion molecules,played an important role during the invasion procession of cancer cells. Many scholars have noticed that except cell adhesion molecules,Claudins(CLDN) also have relationship with the invasion procession of cancer cells,which are proteins maintaining the tight junction between the cells.CLDN is a family of proteins.CLDN was first covered by Furuse etal in1998. Scientists have found more than20kinds of them.CLDN are cross-membrane proteins and they are part of the structure of tight junctions between the normal tissue cells.They have different expression in different tissues and cells.According to foreign research,the occurrence and proliferation of a variety of malignant cancer cells have\relationship with the abnormal expression of CLDN. For example,the expression of CLDN1is abnormally low in both breast cancer tissues and endometrial carcinoma tissues but is abnormally high in the colorectal cancer tissues. The abnoamal expressions of CLDN cause the invasion of HCC cells increased. Someone in Zhejiang University have had a research on the expression of CLDN1in gastric cancers. They have found that the positive expression rate of CLDN1have negative correlation with the cancer diameter,depth of invasion,TNM staging,lymphatic metastasis and distant metastasis. The mechanism of that negative correlation is the abnormal expression of CLDN causes the structure of tight junctions between cells damaged and the connections between cells become loose.So the invasion of HCC cells increased. CLDN family in hepatocellular carcinoma is rarely reported.In this experiment,the expressions of cell surface tight junction proteins, CLDN1and CLDN4in HCC were studied and we analysised the relationship between the expressions of CLDN and clinicopathologic factors.Then we explored the relationship between the expressions of CLDN and the invasion of HCC.ObjectiveThis research is designed to detect the expressions of CLDN1and CLDN4in both hepatocellular carcinoma tissues and normal liver tissues and analyze the differences between the expressions of CLDN in hepatocellular carcinoma tissues and the expressions of CLDN in normal liver tissues.We also researched the relationship between their expressions and biological behaviour of HCC to investigate the function and clinical significance of the CLDN1and CLDN4in the occurrence, infiltration and spreading of HCC cells.Material and methodsThis study collected60paraffin-embedded cases of HCC and50cases of normal liver tissue from Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University during the last two years. Immunohistochemistry method was used to detect the expressions of CLDN1and CLDN4in both hepatocellular carcinoma tissues and normal liver tissues.The relation between CLDN1and CLDN4was evaluated and analysised by SPSS18.0statistics software, The relationships between the expression of CLDN1and CLDN4in HCC and their clinical significance weie discussed.ResultsThe positive expressions of CLDN1and CLDN4are both mainly located in cell surface and accidentally visible at the plasma The positive performance is the diffusing claybank dyeing in the cell membrane. The positive expression rate of CLDN1is70%(42/60) in HCC tissues which is obviously higner than the positive rate0(0/50) in normal liver tissue,(P<0.05). The positive expression of CLDN4is located in cell surface and accidentally visible at the plasma and the positive performance is the grain claybank dyeing. The positive expressions rate of CLDN4is25.00%(15/60) in HCC tissues which is obviously lower than the positive rate100%(50/50) in normal liver tissue,(P<0.05).The expressions of CLDN1had correlation with the expressions of CLDN4in HCC (r=0.533, P<0.05). The expressions of CLDN1and CLDN4were not correlated with the differentiation degree of HCC and the age and sex of HCC patients(P>0.05).Both expressions have nothing to do with tumor quantity,diameter, AFP serum concentration (P>0.05).The expression of CLDN4has associated with the type of HCC and the existing of tumor thrombus.Conclusion1.CLDN1expression in HCC is abnormally high and the expression of CLDN4in HCC is abnormally low. The expressions of CLDN1had correlation with the expressions of CLDN4in HCC.CLDN1gene may be a proto-oncogene for HCC.CLDN4gene may be a tumor suppressor gene.2. The expressions of both CLDN1and CLDN4have nothng to do with the tumor histological differentiation,serum AFP values,sex, age of the patients, diameter and nodule number of HCC. But CLDN4has associated with the type of HCC and the existing of tumor thrombus.3.The abnormal expression of CLDN1and CLDN4in HCC may destroy tight junctions between carcinomar cells and contribute to the spread and metastasis of tumor cells. |
PDF Full Text Request