| Background:Primary liver cancer is one of the clinical common malignant tumor, of which about90%is HCC (Hepatocellular carcinoma, HCC), the global incidence ranks the fifth, also is the second cancer killer in China and the third cause of cancer deaths worldwide. Due to higher malignant degree of liver cancer, the illness progresses quickly, the majority of patients (>80%) are not suitable for surgical resection. Even some of them have resection, the2-year recurrence rate is as high as50%, the prognosis of patients is still poor. Therefore, how to reduce the postoperative recurrence and metastasis of liver cancer in order to further improve the curative effect is one of the research hot spot and difficult point.Hippo pathway was originally discovered in drosophila cells and is a highly conservative regulation inhibitory signal path to the size of the organization. Hippo pathway including:Mstl/2, WW45, Lats and Mobl regulate cell proliferation and apoptosis through Inhibiting Cyclin E, DIAP1(Drosophila inhibitor of apoptosis protein1) and bantam expression involved. YAP is bridging the Hippo pathway and its main physiological effect of downstream protein molecule. The inactivation of Hippo pathway leading to YAP over expression shows up as cell doubling time and cell cycle shortened, increased cell number, excessive proliferation and apoptosis for organization. Research shows that YAP plays an important role in regulation of cell proliferation and apoptosis, control of organ size, cell contact inhibition and the process of tumor. YAP, as a newly discovered oncogene in several solid tumors, is abnormal high expression, and has been reported in liver cancer that high expression of YAP is the independent factors affecting the prognosis of patients with HCC. Otherwise, according to a study that over expression of Mstl in human hepatocellular carcinoma cell line-HepG2cells can lead to increased phosphorylation of YAP and over expression of its downstream protein of connective Tissue Growth Factor (Connective tissue growth factor, CTGF), as an important cytokine regulating activation of HSC biology also has been known for a long time. Most HCC patients have a background of chronic liver disease, and cirrhosis of the liver is the main risk factors for the development of HCC. The activation of Hepatic stellate cells (HSC) has been widely recognised as an important link to the liver fibrosis and cirrhosis. The current study has an obvious found that there are more HSC stay around liver blood sinus cancer cells of distorted primary liver cancer tissue, they are also visible around the cell membrane and focal necrosis of liver cancer, moreover HSC can promote HCC’s proliferation, survival and invasion, its biological effect may be related to the induction of the activation of extracellular regulating kinase (ERK) and NFkappa B. Various cytokines secreted by HSC such as TGF beta, fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor and other factor is likely to be involved, as well as expression of laminin-5(Ln-5) and remodeling of the ECM may be associated with its biological effect to promote tumor growth and invasion.Objective:1. Evaluation of YAP expression in liver cancer tissue effects on tumor recurrence and prognosis2. The movement of YAP in liver cancer tissue expression and potential relationship of HSCMeterial and Methods:227cases of liver cancer tissue samples were analyzed retrospectively by using TMA technology. Immunohistochemical method was applied to observe227cases of YAP expression and102cases of activated HSC in liver cancer and corresponding adjacent liver tissues. The chi-square and the Kaplan-Meier analysis were used to evaluate their impact on tumor recurrence and prognosis, also the potential contact between them.Results:1. The YAP expression in liver cancer tissues is higher and expressed in nucleus predominately, compared with the expression of YAP in adjacent liver tissue which is expressed in the cytoplasm,2. The expression of YAP is significantly associated with cirrhosis of the liver, AFP level, tumor size, tumor capsular, vascular invasion, differentiation degree and the TNM staging but no obvious correlation with sex, age, number of hepatitis b virus surface antigen (HbsAg and tumor had been observed.3. The expression of YAP in carcinoma tissue is an independent risk factors of recurrence and overall survival in HCC patients.4. The expression of YAP in liver cancer tissue and adjacent liver tissue has a certain relevance to the number of activated HSC in adjacent liver tissue, its possible link is: liver cancer cells with YAP over expression secrete more CTGF, which then acts on the adjacent HSC, activate and adjust its functions to promote the secretion of ECM. YAP/TAZ located in cytoplasm of Liver cancer cell can feel increased ECM stiffness in cellular microenvironment and transcribe into the nuclear in response which then cause more production of CTGF, forming a "amplification circuit".Conclusions:1. The YAP expression in liver cancer tissues is higher. It is associated with cirrhosis of the liver, AFP level, tumor size, tumor capsular, vascular invasion, differentiation degree and the TNM staging.2. The expression of YAP in carcinoma tissue is an independent risk factors of recurrence and overall survival in HCC patients.3. The expression of YAP in liver cancer tissue and adjacent liver tissue has a positive correlation with the number of activated HSC in adjacent liver tissue. |
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