title: The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer.
abstract: An increased risk of non-small cell lung cancer (NSCLC) in cystic fibrosis (CF) patients and carriers of CF transmembrane conductance regulator (CFTR) mutations has been proposed. However, the role of CFTR in lung cancer remains controversial. In the present study, CFTR expression was assessed in 165 NSCLC tumors and 22 normal lung samples with validation in an independent series of 131 samples. The effect of gain and loss of CFTR on the malignant behavior of NSCLC was examined. The effect of CFTR manipulation on tumor metastasis was examined in a mouse model. Expression of CFTR was downregulated in NSCLC (p=0.041). Low CFTR expression was correlated with advanced stage (p<0.001) and lymph node metastasis (p=0.009). Low CFTR expression was significantly associated with poor prognosis (overall survival: 45 vs. 36 months, p<0.0001; progression-free survival: 41 vs. 30 months, p=0.007). Knockdown of CFTR in NSCLC cells enhanced malignant behavior (epithelial-mesenchymal transition, invasion and migration); in contrast, overexpression of CFTR suppressed cancer progression in vitro and in vivo. The tumor-suppressing effect of CFTR was associated with inhibition of multiple uPA/uPAR-mediated malignant traits in culture. These results show that CFTR plays a role in inhibition of NSCLC metastasis and suggest that CFTR may serve as a novel indicator for predicting adverse prognosis and metastasis in NSCLC patients.
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
authors.forename: Jie Ting
authors.initials: JT
authors.lastname: Zhang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Fenglan
authors.initials: F
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Juhong
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Catalan Institute of Oncology, Badalona, Catalonia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou, Guangdong, P.R. China.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, P.R. China.
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis*; D018572:Disease-Free Survival; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator