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Expression Of ALK1 In Non-small Cell Lung Cancer And Its Clinical Significance

Posted on:2017-11-25Degree:MasterType:Thesis
Country:ChinaCandidate:D LiuFull Text:PDF
GTID:2334330503967307Subject:Surgery
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Background:Lung cancer is one of the most common cancer in the world,and its mortality is also the highest among the malignant tumors.It is a trend that the mortality and morbidity of lung cancer increase gradually year by year.Male patients rank the first of the highest mortality and morbidity of malignant tumors,while female patients are less than male in this regard.According to statistics,about more than 600,000 people die from lung cancer in China annually,which is a serious threat to life and health of our people.The main treatment for lung cancer currently include surgery, conventional chemotherapy and radiation therapy.The molecular targeted gene therapy of lung cancer has become a heated topic recently,which has achieved great success.Gene-targeted drugs are available one by one,and even has developed to the third generation.But these newly developed drugs are primarily for the same kind of genes such as EGFR, anaplastic lymphoma kinase, etc.Once these genetic locus mutate and get drug resistance,new gene-targeted drugs are on urgent need.Because of this,we are forced to look for some new genetic breakthrough,develop and explore new and effective molecular targets in order to improve tumor targeting therapy.Objective:To research the expression characteristics of ALK1 in TGF-beta signaling pathway of non-small cell lung cancer(NSCLC) tissues from protein and m RNA levels, as well as to explore the effect and Clinical Significance in the occurrence of NSCLC.Methods:The Real-time quantitative-PCR and western blot method were used to detect the gene and protein expression of ALK1 in different non-small cell lung cancer cell Lines, and ALK1 expression levels in 43 cases of NSCLC is determined by quantitative real-time polymerase chain reaction(q RT-PCR) and analyze the relation of clinicopathologic features with ALK1 expression in NSCLC patients. So as to observe the difference in non-small cell lung cancer and normal lung cells.Results:The result of ALK1 gene expression by Real-time PCR shows that ALK1 gene expression in cell lines of A549(0.633±0.068) and H125(0.598±0.022) is significantly higher than the corresponding normal cell lines(0.292±0.014), And the western blot also showed that the ALK1 protein is significantly higher than the normal one.,the ALK1 relative expression in A549 and H125 cell lines is 2.46 and 2.12 times of normal cell lines.ALK1 gene in 72.1%(31/43)shows high expression in NSCLC than the corresponding para-carcinoma tissue. Meanwhile, ALK1 upregulated in NSCLC with cell differentiation degree(P=0.033)and distant metastasis(P=0.031)and TNM stage(P = 0.000) are closely related. And there is no correlation with patients' gender, age, tumor size and number, CEA level and lymph node metastasis.Conclusions:The expression of ALK1 is up-regulated in NSCLC tissues,Indicated that these genes reduce the Inhibition of cancer cells by increase the amount of protein,So the high expression of ALK1 in TGF-beta signaling pathway has Close relationship with the NSCLC, Providing a new underlying direction of targeted therapy or being a new tumor marker in serum for the NSCLC.
Keywords/Search Tags:NSCLC, TGF-beta signaling pathway, quantitative real-time polymerase chain reaction(qRT-PCR), western blot, ACVRL1, Alk1, targeted therapy
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