The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer
Adult
Male
Mice, Inbred BALB C
Epithelial-Mesenchymal Transition
Lung Neoplasms
Blotting, Western
Cystic Fibrosis Transmembrane Conductance Regulator
Down-Regulation
Mice, Nude
Kaplan-Meier Estimate
Middle Aged
Immunohistochemistry
Disease-Free Survival
3. Good health
Mice
03 medical and health sciences
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
Biomarkers, Tumor
Animals
Humans
Female
Aged
DOI:
10.3892/ijo.2015.2921
Publication Date:
2015-03-06T13:33:14Z
AUTHORS (16)
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.
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CITATIONS (43)
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