The cystic fibrosis transmembrane conductance regulator as a biomarker in non-small cell lung cancer

• DOI: 10.3892/ijo.2015.2921
• Publication Date: 2015-03-06T13:33:14Z
• Authors: JIN LI; JIE TING ZHANG; XIAOHUA JIANG; XIAOSHUN SHI; JIANFEI SHEN; FENGLAN FENG; JINGYI CHEN; GUIHONG LIU; PING HE; JUHONG JIANG; LAI LING TSANG; YAN WANG; RAFAEL ROSELL; LONG JIANG; JIANXING HE; HSIAO CHANG CHAN
• Keywords: 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

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.