Expression Of Livin In Non Small Cell Lung Cancer Tissues And The Mechanism Of Its Resistance To Apoptosis

[Background] : It is suggested Livin,a novel inhibitor of apoptosis protein(IAP),be overexpressed in a variety of carcinomas including lung cancer,which might be associated with neoplasm development,such as anti-apoptosis.However,its mechanism still remains to be clarified in future,regarding to its effect upon malignant cells to resistant apoptosis.It could be served as a potenial target for cancer treatment with current evidence of investigation.[Objective]:To explore the expression of Livin by lung cancer,lung benign tissues,and the relationship between Livin expression and its clinical characteristics .To study the associability of expression between Livin and each key factor in anti-apoptosis pathway of Livin(such as Bcl-2,Pro-Caspase-3,Cleaved-caspase-3,dephosphorylation JNK1,phosphorylation JNK1).And analyze the prognosis of the lung cancer patients and assess the risk factor of prognosis.[Methods]:The expression of Livin protein,Bcl-2 protein,Pro-caspase-3 protein,Cleaved-caspase-3 protein,dephosphorylation JNK1 protein and phosphorylation JNK1 protein were evaluated by immunohistochemical two-step methods and SABC methods,meanwhile evaluate LivinmRNA,Caspase-3mRNA by hubridization in situ method. And the data of result were analyed by chi square test,kappa test,spearman's rank correlate,cox regression and Kaplan-Meier survival study.[Result]:1 The expression of Livin,Pro-caspase-3,Cleaved-caspase-3 and dephosphorylation JNK1 were only detected in the endochylema.While most of phosphorylation JNK1 protein were deteced in the endochylema,some were detected in the nucleus.2.The positive expression rate of Livin protein in lung cancer was 65.78%,which expressed abundances were much higher than those expressed in benign lung tissues(0.00%)(P<0.01). It suggests more NSCLC tissues show expreesion of Bcl-2 than in lung benign tissues(70.05% versus 0.0%),less NSCLC tissues show expreesion of Pro-caspase-3 than in lung benign tissues( 64.17% versus 87.5% ) , less NSCLC tissues show expreesion of dephosphorylation JNK1 than in lung benign tissues(46.5% versus 70%),more NSCLC tissues show expreesion of phosphorylation JNK1 than in lung benign tissues(58.29% versus 40.00%).3.The positive expression rates of Livin in squamous carcinoma,adenocarcinoma and other carcinoma were 74.07%,61.96%,42.86%,and the difference is of significance in statistics science. The positive expression rates of Bcl-2 in squamous carcinoma,adenocarcinoma and other carcinoma were 77.78%,67.39%,42.86%,and the difference is of significance in statistics science. The positive expression rates of Pro-caspase-3 in squamous carcinoma,adenocarcinoma and other carcinoma were 51.82%,76.09%,57.14%,and the difference is of significance in statistics science. The positive expression rates of phosphorylation JNK1 in squamous carcinoma,adenocarcinoma and other carcinoma were 61.73%,52.17%,78.57%,and the difference is of significance in statistics science.4 The expression of Livin was positive correlated with Bcl-2 expression(r=0.414,p=0.0000). The expression of Livin was not correlated with Pro-caspase-3 expression(r=-0.116,p=0.114). The expression of Livin was negative correlated with Cleaved-caspase-3 expression.(r=-0.168,p=0.021) The expression of Pro-caspase-3 was positive correlated with cleaved-caspase-3 expression(r=0.191,P=0.009), The expression of Livin was not correlated with dephosphorylation JNK1 expression(r=-0.050,P=0.494),The expression of dephosphorylation JNK1 was negative correlated with phosphorylation JNK1 expression(r=-0.146,P=0.046)。5. Lymph node metastasis is an individual factor affecting the prognosis of lung cancer operated patients .But age,sex,tumor size,tumor position,Livin,Bcl-2,Pro-caspase-3,Cleaved-caspase-3,dephosphorylation JNK1,phosphorylation JNK1 have not significant correlation with patients prognosis.6. LivinmRNA,Caspase-3mRNA were only detected in the endochylema but none was detected in nucelus.The expression of LivinmRNA,Caspase-3mRNA in lung cancer have not significant correlation with age,sex,cell differentiation,Lymph node metastasis,TNM staging,tumor size and tumor position.7.The positive expression rate of LivinmRNA in lung cancer was 50.00%,which expressed abundances were much higher than those expressed in benign lung tissues(P<0.01). The positive expression rate of Caspase-3mRNA in lung cancer was 42.42%,which expressed abundances were much lower than those expressed in benign lung tissues(P<0.01). The expression of LivinmRNA was negative correlated with Pro-caspase-3mRNA expression.(r=-0.368,P=0.002).8.The survival rate of the patients who were positive expressed LivinmRNA is about 30.30%,while the survival rate of the patients who were negative expressed LivinmRNA is about 69.70%. ,and the difference is of significance in statistics science.Meanwhile, The survival rate of the patients who were positive expressed Livin protein is about 41.5%,while the survival rate of the patients who were negative expressed Livin protein is about 64.0%, and the difference is not of significance in statistics science.But the difference of the survival rate of the patients between one year and five years after operation is of significance. [Conclusion]:1.The positive expression of LivinmRNA and Livin protein in lung cancer tissues were much higher than those expressed in benign lung tissues,at the same time ,combing the result of the expriment of Livin and other IAP members in vitro.,it is suggested that Livin may play improtant role in the carcinogenesis and development of lung cancer through inhibiting cell apoptosis.So it is possible that Livin can be a new tumor marker of lung cancer diagnosis and the new target of tumor treament.2.The different expression of Pro-caspase-3 and Cleaved-caspase-3 in lung cancer tissues and benign lung tissues means the low expression of Pro-caspase-3 and Cleaved-caspase-3 have something with the development of lung cancer.It also hint that they play improtant roles in the malignant transformation of lung cancer cell and the carcinogensis and development of lung cancer.3. Dephosphorylation JNK1 expressed abundances in benign lung tissues were higher than in lung cancer tissues.And it cued that there is the pneumona of dephosphorylation JNK1 down regulation during the carcinogensis and development of lung cancer .However, phosphorylation JNK1 expressed abundances in lung cancer tissues was much higner than benign lung tissues.It cued that different JNK1 may take part in the opposite activation mechanisms in the carcinogensis of lung cancer. 4. In the carcinogensis of lung cancer,Livin maybe mainly directlyinhibited caspase-3(including Pro and Cleaved) in the downstream level;Bcl-2 mainly indirectly inhibited caspase-3(including Pro and Cleaved) in the upstream level .The anti-apoptotic pathway of Livn and Bcl-2 maybe converged on caspase-3 (including Pro and Cleaved) Livin chiefly inhibit Cleaved-caspase-3,while lighitly inhibit Pro-caspase-3.The activation of Cleaved-caspase-3 depends on Pro-caspase-3. The processing of Livin inhibiting Pro-caspase-3 and inhibiting Cleaved-caspase-3 commonly coexist in the same cell.5. Dephosphorylation JNK1 was detected in the endochylema but none was detected in nucelus.,while most of phosphorylation JNK1 protein were deteced in the endochylema,some were detected in the nucleus. Phosphorylation JNK1 protein quickly assembles in the mucleus once they received activation signial,and then induce expression alteration of some genes. The nucelus expression of phosphorylation JNK1 maybe a significant marker of judging the prognosis of lung cancer,and the positive expression of it hints good prognosis.Meanwhile,it also provide indirect evidences that JNKs pathway play great roles in the carcinogensis and development of lung cancer.6.The expression of LivinmRNA was correlated with the prognosis of lung cancer patients,while the expression of Livin protein maybe correlated with the prognosis of lung cancer patients.