Abstract
Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines. Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways. NSCLC patients at advanced stage (N=150) who received EGFR-TKIs (gefitinib or erlotinib) as second- or third-line therapy from September 2008 to December 2012 were included in the study. In 66 NSCLC patients with wild-type EGFR, high levels of miR-200c expression was associated with higher disease control rate (DCR), longer progression-free survival (PFS) and longer overall survival (OS) compared with low miR-200c expression subgroup. In the subgroup with EGFR mutation, the trend remained the same but not statistically significant. Overall, these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR.
Highlights
Lung cancer is the leading cause of cancerrelated mortality worldwide and non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer [1]
The results showed that miR-200c expression was decreased, and ZEB1, the potent target of miR-200c was increased in all 5 primary resistant NSCLC cell lines, compared with PC9 (Figure 1B, 1C)
We observed that miR-200c regulated Epithelial-to-mesenchymal transition (EMT) by targeting ZEB1 in NSCLC cell lines and high expression of miR-200c can increase sensitivity to gefitinib
Summary
Lung cancer is the leading cause of cancerrelated mortality worldwide and non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer [1]. With the identification of several oncogenic drivers, personalized therapy has gained prominence in patients with advanced NSCLC. Only minority patients have these driver mutations. About 3–5% of NSCLC patients harbor ALK-rearrangement [5,6,7], and about 30–40% East Asian patients harbor EGFR mutation (EGFR-MUT) [8,9,10]. Though the majority of NSCLC patients were EGFR wild type (EGFR-WT), there are still 3–15% of them respond to EGFR-TKIs with a disease control rate (DCR) of 40–60% [8, 11,12,13], which suggests that www.impactjournals.com/oncotarget a subgroup of EGFR-WT patients benefit from EGFR inhibitor treatment. To achieve optimal outcomes, EGFR-WT patients who may benefit from EGFR-TKIs treatment should be identified
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
