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
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (38)
CITATIONS (43)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....