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The Expression And Significance Of Angpt1-3,avβ3 In Non-small Cell Lung Cancer

Posted on:2011-02-16Degree:MasterType:Thesis
Country:ChinaCandidate:C Y ShenFull Text:PDF
GTID:2154330332458143Subject:Surgery
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Background and objectivesLung cancer, as one of the most common malignacies in the world, has become a leading cause of cancer death in most countries. So it has been regarded as the most harmful malignancy to human life. In our country, the incidence and mortality rates of lung cancer have been increasing. It is investigated that in recent years lung cancer with its death rate of 22.7% has replaced live cancer ranking the first death cause among the top ten malignacies. Lung cancer has been listed as one of the important scientific study in China, for its annual increase of incidence is up to 26.9%. Therefore, a new thorny subject confronting the medical workers is how to discover lung cancer at its early stage so as to improve its treatment effect and prolong the life span of the patients. In those years, the big improvements have been made in many aspects such as the diagnosis and treatment of lung cancer and survival rate of the patients after treatment. However, until now the overall cure rate of lung cancer is still below 15%. It has been proved that distant metastasis and local recurrence of lung cancer are the main factors causing the curative effect and prognosis after operation. And often tumor growth and metastasis directly lead to the death of the patients. For this reason, the researchers have made countless studies towards tumor growth and metastasis. A great number of studies show that tumorus angiogenesis is not only closely related to but the basis of tumor growth, infiltration and metastasis. A great attention has been paid to tumorus angiogenesis for its role in the occurrence and development of cancer. At present, the study on angiogenesis mainly focuses on vascular endothelial growth factor (VEGF) and its receptor system. But in recent years another family system has been discovered, angiopoietin-like protein, and has been drawn much attention with its receptor system as well.Angiopoietin-like protein 3 is a kind of secretary glycoprotein and also a member of angiopoietin-like protein family. It was just found in searching a new kind of angiopoietin and got its name for having glycoprotein in common with other members in angiopoietin-like protein family. However, it has unique structure slightly distinguished from other members, which might be produced by inducing vessels by combining with receptor of Integrinαvβ3.Integrins are kind of cell adhension molecules (CAMs) and the main factors to mediate attachment between a cell and the extracellular matrix (ECM). they can not only mediate the adhensiveness between vascular endothelial cell and tumor cell, but also get involved in angiogenesis and tumor metastasis. Connecting cell and ECM. integrins are important receptors that help the attachment of cell to the ECM and inside the cells. Among the integrin family, integrinαvβ3 is evidently important to angiogenesis. Studies show that integrin av(33 has close connections with tumor growth, penetration, metastasis, especially angiogenesis induced by tumor.Studies at present carried out more focus on new angiogenesis induced by avP3, but less on new angiogenesis produced by Angptl-3, not to mention their inter-relationships. In the experiment, RT-PCR is employed to determinate two tumor markers which are closely related to the tumorigenesis, invasion and metastasis of tumor, while analyzing the gene expression of Angptl-3,αvβ3 in nonsmall-cell lung cancer, NSCLC and even making a further analysis of their relations in NSCLC to discuss its significance in clinical pathology. The experiment helps to have a deep understanding of the invasion and metastasis of tumor and provides a theoretical basis for diagnosis and treatment of lung cancer as well.Methods 1.50 cancer tissues and 50 adjacent normal tissues are obtained from the patients with NSCLC who underwent resection in our hospital from Feb. to Jun. in 2009. All cases with complete clinical data and pathologic diagnosis are not cured with chemotherpy and radiotherapy.2. RT-PCR is employed to determinate the gene expression of Angptl-3,αvβ3 in the 50 cases cancer tissue and 50 cases adjacent normal tissues, while analysing the relationship of gene expression of Angptl-3,αvβ3 and clinical pathological feature in cancer tissues.3. SPSS 10.0 software application is used for all analysis, and statistical significance is defined as a values equaling to 0.05.Results1. The mean expression of Angptl-3mRNA in cancer tissues is significantly higher than that in nomal lung tissues(0.894±0.571,0.187±0.256, P<0.05).2. The mean expression of Angptl-3mRNA in the poorly differentiated and undifferentiated cancer tissue is significantly higher than that in the well-differentiated, moderately differentiated cancer tissue. (1.236±0.528, 0.719±0.517, P<0.05); Increased abundance of Angptl-3mRNA is relative to lung cancer TNM stage. The latter lung cancer stage is, the higher Angptl-3mRNA expresses(P<0.05). But their relations to the category of tumor, sex and age are not significant(P<0.05).3. The mean expression of av subunit andβ3 subunit mRNA in cancer tissues is significantly higher than that in nomal lung tissues(0.802±0.590 0.804±0.629, 0.128±0.219 0.170±0.296,P<0.05).4. The mean expression of av subunit andβ3 subunit mRNA in the poorly differentiated and undifferentiated cancer tissue is significantly higher than that in the well-differentiated, moderately differentiated cancer tissue(1.077±0.699 1.102±0.735, 0.660±0.477 0.651±0.514, P<0.05)creased abundance of Angptl-3mRNA correlates with lung cancer TNM stage. The latter lung cancer stage is, the higher Angptl-3mRNA expresses (P<0.05). But their relations to the category of tumor, sex and age are not significant(P<0.05).5. There is a significantly positive correlation between Angptl-3mRNA and av subunit mRNA(r=0.538, P<0.05). Similarly, positive correlation exists between Angptl-3mRNA andβ3 subunit mRNA(r=0.776, P<0.05), and also between av subunit mRNA andβ3 subunit mRNA(r=0.686,P<0.05).Conclusions1. There is excessive expression of Angptl-3 and avP3mRNA in NSCLC tissues, and a significant positive correlation between them.2. Homo-expression of Angptl-3 andαvβ3mRNA closely correlated with lung cancer TNM stage and degree of differentiation. They may be used to evaluate the biological behavior and predict invasion and metastasis of NSCLC.3. Angptl-3 andαvβ3 may be important targets for antigiogenesis therapy in patients with NSCLC.
Keywords/Search Tags:NSCLC, Angptl-3, αvβ3, Angiogenesis
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