The Expression And Clinical Significance Of YAP And P-YAP In Hepatocellular Carcinoma

Objective: Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer, and it is one of the most common malignant tumor diseases in our country and around the world. As one of the most diseases of the world, HCC usually was found when patients had access to later period. The effect of conventional chemotherapy on HCC is not obvious to the survival rate and significantly lower than other cancers. So consolidating the basic and clinical research of HCC, and finding out more liver cancer genes and tumor suppressor genes and clearing the relationship in HCC has become an important direction of current research.As a novel signal transduction pathway, the Hippo pathway plays an important role in promoting apoptosis, limiting cells proliferation and regulating organ size. Yes-associated protein(YAP) is the effector in downstream of the Hippo pathway and participates cell signal transduction to control the cells multiplication and apoptosis balance in phosphorylated form(P-YAP). In pathological conditions, the Hippo pathway on YAP phosphorylation failure breaks the balance in cellular proliferation and apoptosis, Leads to tissue and organ overgrowth and tumorigenesis. Studies on the related animal experiment at home and abroad demonstrate that YAP is involved in the formation and development of gastric cancer, colon cancer, lung cancer and other tumors. Primary hepatocellular carcinoma patients were used as the research object. The expression of YAP and P-YAP were detected by immunohistochemistry and western blot in three groups. The relationship between expression of YAP and age, tumor size, AFP level, differentiation degree and the TNM staging were researched in our study. The important function and significance of YAP was revealed in the development of HCC. This theory provides a theoretical basis for the clinical treatment of liver cancer.Method: 78 pecimens of HCC patients with complete clinical and pathological data after curative resection were collected from the department of hepatobiliary surgery in Tangshan Worker’s Hospital during Aug. 2012 to Jul. 2014. The specimens were divided into two copies. One was made a neutral formalin fixed purchase paraffin to use for HE staining and immunohistochemistry, the other fresh tissue was used for Western blot. Morphology changes of three kinds of tissues were observed in different multiples under the microscope by HE staining. The expression of YAP, P- YAP in the three specimens was identified by immunohistochemistry with SP method. YAP, P- YAP protein were detected by western blot. The relationship between YAP and HCC patient age, tumor size, pathology classification, transfer and TNM staging was analysed by Chi-square. Correlation analysis between YAP and P-YAP expression in each group was analysed with Pearson test.Results:1 HE stain results indicated: The structure of hepatic lobule in normal liver tissues was clear, liver cells arranged tightly and orderly as cords. Central vein and multiple capillary sinus were visible. The normal structure of hepatic lobule in liver cirrhosis tissues was destroyed, liver cells arranged in disorder with the larger volume and a hyperchromatic nuclei. There were lots of inflammatory cells and fibrous tissue in hepatic lobule. Liver organization in cancer loses the normal structure of hepatic lobule. Cancer cells and their nucleus became larger with inconsistent size and shape. The multinucleated and atypical nuclei were significant basophilic. Multiple capillary sinus were broadened.2 The results of immunohistochemistry indicated: P-YAP in normal liver tissues expressed strongly in cytoplasm. The positive expression rate in cirrhosis was lower than control group and no expression of P-YAP in cancer tissue. Opposite to P-YAP,strong positive expression of brown yellow was identified in nucleus and cytoplasm of hepatocellular carcinoma cells. Positive expression was identified in cirrhosis and no nuclear expression in normal tissue.3 The results of western blot indicated that expression of P-YAP protein in normal liver tissues was significantly higher than liver cancer tissues and the differences had statistically significant. Along with the evolution of normal to cancer tissues, the expression of YAP protein increased obviously. The expression in cancer tissues was significantly higher than other two groups(P<0.05).4 The expression of YAP is significantly associated with AFP level, differentiation degree and the TNM staging but no obvious correlation with age and tumor size.5 The expression of P-YAP protein decreased when the YAP increased. The two variables are negative correlation.Conclusions:1 There is almost no expression of P-YAP in HCC but strong expression of YAP proves that YAP plays an important role in the occurrence and development of tumor and provides important clues in early detection and diagnosis in clinical cancer.2 The expression of P-YAP protein decreased when the YAP increased. The two variables are negative correlation.3 The expression of YAP is significantly associated with AFP level, differentiation degree and the TNM staging but no obvious correlation with age and tumor size.