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- Title
A miRNA Panel Predicts Sensitivity of FGFR Inhibitor in Lung Cancer Cell Lines.
- Authors
Shengxiang Ren; Rivard, Christopher J.; Hui Yu; Genova, Carlo; Rozenboom, Leslie; Dexiang Gao; Hinz, Trista K.; Rikke, Brad A.; Wynes, Murry W.; Caldwell, Charles; Agustoni, Francesco; Kenichi suda; Tao Jiang; Caicun Zhou; Heasley, Lynn E.; Hirsch, Fred R.; Ren, Shengxiang; Yu, Hui; Gao, Dexiang; Jiang, Tao
- Abstract
<bold>Purpose: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
ANTINEOPLASTIC agents; BENZAMIDE; CELL physiology; CELL receptors; CELLULAR signal transduction; COMPARATIVE studies; HETEROCYCLIC compounds; IMIDAZOLES; LUNG cancer; LUNG tumors; RESEARCH methodology; MEDICAL cooperation; RESEARCH; RESEARCH funding; RNA; EVALUATION research; CANCER cell culture; PHARMACODYNAMICS
- Publication
Clinical Lung Cancer, 2018, Vol 19, Issue 5, p450
- ISSN
1525-7304
- Publication type
journal article
- DOI
10.1016/j.cllc.2018.06.004