Expression Of Livin And Caspase 9 And Their Correlation In Human Non-small Cell Lung Carcinoma

Background: Lung cancer is one of the most common malignant tumors in human, and is the main cause of cancer death. It is severely threatening human's health. The mechanism of cancer is a complicated processing related to many genes, stages, and the unbalance of cell multiplication and cell apoptosis. Inhibitor of apoptosis protein (IAP) is a group of endogenous inhibitory factor. The over-expression of IAP will cause reduced apoptosis, which is closely related with the tumor development.Livin is a novel inhibitor of apoptosis protein. Livin could be detected in most human solid tumor cell and has a strong role in inhibiting apoptosis. Caspase (Cysteinyl-spartate specific protimase) family is the implementation of the main enzymes of apoptosis. Activated Caspase can degrade of the functional protein and structural protein of cells, and cause apoptosis. The expression of Caspase 9 (a start-up factor of the Caspase family) in lung cancer was seldom studied till now. Livin has been identified containing a single Baculoviral IAP Repeats (BIR) domain. Similar to other IAP family members, the anti-apoptotic activity of Livin is dependent on the BIR domain. The domain mediates direct interaction between Livin and Caspase 3, 7and 9, thereby blocking the active form of the downstream caspases and inhibiting apoptosis. Recently, many studies have focused on the specific over-expression of Livin in non-small cell lung cancer. However, the correlation between the expression of Livin and NSCLC patients with pathological type, tumor differentiation, lymph node metastasis and TNM stages has not been fully elucidated. The relationship between Livin and oncogenes, tumor suppressor genes and other apoptosis-related genes in lung cancer is not yet clear. As a possibile molecular marker of NSCLC, Livin may become a new target for diagnosis and treatment of NSCLC, and has drawn more attention.Objective: To detect the expression of Livin and Caspase9 proteins in non-small cell lung carcinoma (NSCLC) tissues, adjacent tissues, and normal lung tissues, discuss the role of the two proteins in NSCLC development by analyzing the correlation between them. The experiments base for Livin as lung cancer molecular markers used in clinical will be provided.Methods: The expression of Livin and Caspase9 proteins was detected by streptavidin-peroxidase immunohistochemistry method in 58 cases of NSCLC and 50 pericarcinomatous tissues, 8 normal lung tissues. Expression of these proteins was analyzed for correlation with histological typing, degree of differentiation, clinical stage and lymph node metastasis.Results: The positive expression rate of Livin protein in NSCLC (65.5%) was significant higher than those in adjacent tissues (26.0%, P<0.05) and normal lung tissue (0%, P<0.05). Livin protein expression in adenocarcinoma (87.5%) was significantly higher than in squamous cell carcinoma (46.5%, P<0.05) and adenosquamous carcinoma (66.7%, P<0.05). The positive expression rate (83.3%) of Livin protein in lymph node metastasis is higher than in the non-lymph node metastasis (46.4%, P<0.05). The positive expression rate of Livin protein in NSCLC tissue was related with histological typing and lymph node metastasis significantly (P < 0.05), except that the differentiation degree and clinical stage (P > 0.05). The positive expression rate of Caspase9 protein in NSCLC (31.0%) was significant lower than those in adjacent tissues (82. 5%, P<0.05) and normal lung tissue (87.5%, P < 0.05). The positive expression rate of Caspase9 protein in NSCLC tissue was significant related with lymph node metastasis (P<0.05), except the differentiation degree, clinical stage and histological type (P>0.05). The expression of Livin protein was negatively related to that of Caspase9 protein in NSCLC tissues (R2 = 0.1447, P=0.003).Conclusions:1. Livin protein mainly located in cytoplasm and highly expressed in NSCLC. The positive expression is correlated with pathological type of lung cancer and lymph node metastasis. These results suggest that Livin may be involved in lung cancer, especially in adenocarcinoma by a mechanism and is expected as a molecular marker used in the diagnosis and treatment of lung cancer.2. The positive expression of Caspase9 protein in NSCLC was significantly lower than normal lung tissue and adjacent to cancer and normal lung tissue. It suggests that the loss expression of Caspase9 protein may play an important role in lung carcinomas and its progression.3. The expression of Livin protein is negatively related to that of Caspase9 protein in NSCLC tissues. Livin protein may inhibit cell apoptosis and promote cell proliferation by inhibiting the activity of Caspase9 protein, therefore accelerate the normal cell malignant transformation, resulting in the occurrence of lung cancer development and progression.