We investigated whether microRNAs (miRNAs) may serve as an alternative biomarker of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor (TKI) sensitivity in lung cancer cell lines. A miRNA panel (let-7c, miRNA155, and miRNA218) could be useful in predicting response to FGFR TKIs, either ponatinib or AZD4547. Purpose: To test whether a microRNA (miRNA) panel may serve as an alternative biomarker of fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor sensitivity in lung cancer. Methods: Histologically diverse lung cancer cell lines were submitted to assays for ponatinib and AZD4547 sensitivity. miRNAs, FGFR1 messenger RNA, gene copy number, and protein expression were detected by real-time quantitative PCR, fluorescence in-situ hybridization, and immunoblotting in 34 lung cancer cell lines. Results: Among 34 cell lines, 14 exhibited ponatinib sensitivity and 20 exhibited AZD4547 sensitivity (drug concentration causing 50% inhibition values < 100 nmol/L). A total of 39 of the 377-miRNA set were initially identified from the 4 paired ponatinib-sensitive or -insensitive cell lines to have at least an 8-fold differential expression and then were detected in all the 34 cell lines. A predictive panel of 3 miRNAs (let-7c, miRNA155, and miRNA218) was developed that had an area under the curve (AUC) of 0.886 with a sensitivity of 71.4% and specificity of 77.3% to predict response to ponatinib. The miRNA panel performed similar to FGFR1 protein expression (AUC = 0.864) and messenger RNA expression (AUC = 0.939), and better than FGFR1 amplification (AUC = 0.696). Furthermore, we validated this panel using data for sensitivity to AZD4547 in the cell line cohort with an AUC of 0.931 and a sensitivity of 73.3% and specificity of 76.2%, respectively. Conclusion: The developed miRNA panel (let-7c, miRNA155, and miRNA218) may be useful in predicting response to FGFR tyrosine kinase inhibitors, either ponatinib or AZD4547 in lung cancer cell lines, and warrants further validation in the clinical setting.
|Titolo:||A miRNA Panel Predicts Sensitivity of FGFR Inhibitor in Lung Cancer Cell Lines|
|Data di pubblicazione:||2018|
|Appare nelle tipologie:||01.01 - Articolo su rivista|
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