| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lovat, Francesca Minuti, Gabriele Gasparini, Pierluigi Landi, Lorenza Carasi, Stefania Tibaldi, Carmelo Fassan, Matteo D'incecco, Armida Croce, Carlo M. Cascione, Luciano Chella, Antonio Cappuzzo, Federico Alì, Greta Fontanini, Gabriella |
| Description |
Author Affiliation: Gasparini P ( Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210); Cascione L ( Lymphoma and Genomics Research Program, Institute of Oncology Research, CH-6500 Bellinzona, Switzerland); Landi L ( Department of Oncology, Tuscan Tumor Institute (ITT), 57100 Livorno, Italy); Carasi S ( Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210); Lovat F ( Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210); Tibaldi C ( Department of Oncology, Tuscan Tumor Institute (ITT), 57100 Livorno, Italy); Alì G ( University Hospital of Pisa, 56126 Pisa, Italy); D'Incecco A ( Department of Oncology, Tuscan Tumor Institute (ITT), 57100 Livorno, Italy); Minuti G ( Department of Oncology, Tuscan Tumor Institute (ITT), 57100 Livorno, Italy); Chella A ( University Hospital of Pisa, 56126 Pisa, Italy); Fontanini G ( University Hospital of Pisa, 56126 Pisa, Italy); Fassan M ( Department of General Anatomic Pathology, University of Padua, 35100 Padova, Italy.); Cappuzzo F ( Department of Oncology, Tuscan Tumor Institute (ITT), 57100 Livorno, Italy); Croce CM ( Comprehensive Cancer Center, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210); |
| Abstract |
microRNAs (miRNAs) can act as oncosuppressors or oncogenes, induce chemoresistance or chemosensitivity, and are major posttranscriptional gene regulators. Anaplastic lymphoma kinase (ALK), EGF receptor (EGFR), and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are major drivers of non-small cell lung cancer (NSCLC). The aim of this study was to assess the miRNA profiles of NSCLCs driven by translocated ALK, mutant EGFR, or mutant KRAS to find driver-specific diagnostic and prognostic miRNA signatures. A total of 85 formalin-fixed, paraffin-embedded samples were considered: 67 primary NSCLCs and 18 matched normal lung tissues. Of the 67 primary NSCLCs, 17 were echinoderm microtubule-associated protein-like 4-ALK translocated (ALK(+)) lung cancers; the remaining 50 were not (ALK(-)). Of the 50 ALK(-) primary NSCLCs, 24 were EGFR and KRAS mutation-negative (i.e., WT; triple negative); 11 were mutant EGFR (EGFR(+)), and 15 were mutant KRAS (KRAS(+)). We developed a diagnostic classifier that shows how miR-1253, miR-504, and miR-26a-5p expression levels can classify NSCLCs as ALK-translocated, mutant EGFR, or mutant KRAS versus mutation-free. We also generated a prognostic classifier based on miR-769-5p and Let-7d-5p expression levels that can predict overall survival. This classifier showed better performance than the commonly used classifiers based on mutational status. Although it has several limitations, this study shows that miRNA signatures and classifiers have great potential as powerful, cost-effective next-generation tools to improve and complement current genetic tests. Further studies of these miRNAs can help define their roles in NSCLC biology and in identifying best-performing chemotherapy regimens. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
48 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-12-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Carcinoma, Non-Small-Cell Lung Metabolism Lung Neoplasms MicroRNAs Biosynthesis Proto-Oncogene Proteins P21(ras) RNA, Neoplasm Receptor Protein-Tyrosine Kinases Receptor, Epidermal Growth Factor Animals Drug Therapy Genetics Mortality Pathology Disease-Free Survival Gene Expression Regulation, Neoplastic Classification Survival Rate Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
