Expression Of Cystic Fibrosis Transmembrane Conductance Regulator And Its Correlation With Prognosis In Non-small Cell Lung Cancer

Background Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-relative death worldwide.Most of which are non-small cell lung cancer(NSCLC).Until now the radical surgical resection is the most effective treatment for early stage NSCLC.Early detection and treatment could prolong the overall survival time of patients with NSCLC.However,many of them would be recurrence and occur postoperative metastasis,even after radical resection,including lung,liver,bone,brain and other organs,which is a key factor of the prognosis.Therefore,the study of metastasis mechanisms for NSCLC is particular important.The cystic fibrosis transmembrane conductance regulator(CFTR)is a c AMP-activated anion channel which is expressed ubiquitously in epithelial tissues.Germline mutations in the gene encoding CFTR cause recessive cystic fibrosis(CF).Over the last three decades,long-term survival rate for CF patients has significantly improved but an elevated risk of cancer is being recognized to be associated with survivorship.Intriguingly,an increased risk of cancer,primarily of the gastrointestinal tract,has been reported in some,but not all studies in the carriers of CFTR mutations.Hypermethylation of the CFTR promoter is frequently seen in a number of different tumor types,including lung cancer,suggesting DNA methylationmediated transcription silencing of CFTR may influence cancer development.Of note,both mutation and hypermethylation of CFTR have been identified in NSCLC patients.By analyzing a series of tumors from 296 lung cancer patients from the first affiliated hospital of Guangzhou Medical University,we have shown that aberrant CFTR expression level is significantly associated with NSCLC progression,metastasis and poor prognosis.We provided the theory basis for predicting prognosis for clinical application of CFTR targets for treatment of NSCLC.The knocked down CFTR gene in lung cancer cell A549 was constructed by lentivirus mediated gene silencing technology.We prepared this for further investigation.Object 1.QPCR was applied to detect the m RNA expression of CFTR in patients with NSCLC.Evaluating the correlation between CFTR and the clinical characteristics.2.The knocked down CFTR gene in lung cancer cell A549 was constructed by lentivirus mediated gene silencing technology.Method 1.QPCR was applied to detect the m RNA expression of CFTR in 165 NSCLC tissues and 22 normal tissues.Then we validated the result in 131 NSCLC.2.The knocked down CFTR gene in lung cancer cell A549 was constructed by lentivirus mediated gene silencing technology.QPCR and Western blot were used to validate the discrepancies in m RNA and protein,respectively.Results 1.From the results of q PCR,we found that the expression of CFTR m RNA in NSCLC was much lower than that in normal tissues(p=0.041).The a gradual decrease in CFTR transcripts levels was observed through stage I to IV patients(p<0.001).2.Establishing the knockdown CFTR A549 cell model successfully.Conclusion These results suggest that CFTR gene in NSCLC plays an important role in the process of development.We found that the expression of CFTR m RNA in NSCLC was much lower than that in normal tissues.Results suggest the low expression of CFTR may indicate poor prognosis in patients with NSCLC.So we can deduce CFTR as a new biological predictor to guide the treatment and prognosis of patients with lung cancer management.In order to further explore its role in the tumor cells,we established a stable cell line model of CFTR silence,to prepare for the study of the cellular function and signaling pathways.