Unique microRNA‐profiles in EGFR‐mutated lung adenocarcinomas

• Published in: International journal of cancer Vol. 135; no. 8; pp. 1812 - 1821
• Main Authors: Bjaanæs, Maria Moksnes, Halvorsen, Ann Rita, Solberg, Steinar, Jørgensen, Lars, Dragani, Tommaso A., Galvan, Antonella, Colombo, Francesca, Anderlini, Marco, Pastorino, Ugo, Kure, Elin, Børresen‐Dale, Anne‐Lise, Brustugun, Odd Terje, Helland, Åslaug
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15-10-2014; Wiley Subscription Services, Inc; BlackWell Publishing Ltd
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma of Lung; Aged; Biological and medical sciences; Biomarkers; Cancer; Cancer Genetics; Cohort Studies; DNA Mutational Analysis; EGFR; ErbB Receptors - genetics; Female; Gene expression; Humans; Kaplan-Meier Estimate; KRAS; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Male; Medical research; Medical sciences; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Oligonucleotide Array Sequence Analysis; Pneumology; Proportional Hazards Models; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; survival; Transcriptome; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; RNA interference; Respiratory disease; Lung cancer; Micro RNA; Malignant tumor; Bronchopulmonary adenocarcinoma; Survival; Epidermal growth factor receptor; EGFR; K ras Gene; Gene silencing; Cancerology; C-Onc gene; Bronchus disease; microRNA; KRAS; Mutation; Protooncogene; Cancer; lung cancer; survival
• DOI: 10.1002/ijc.28828
• EISSN: 1097-0215
• ISSN: 0020-7136

The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post‐transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR‐ and KRAS‐mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT‐qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR‐mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR‐mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course.
What's new?
Precise molecular mechanisms for the altered expression of microRNAs in lung cancer are unclear. Here, the authors analyzed microRNA expression in a large sample set of lung adenocarcinomas and corresponding normal lung tissue. They identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal tissue and are thus potential biomarkers for early detection. They found microRNAs differentially expressed between EGFR‐mutated and EGFR wild‐type lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. Moreover, miR‐500a* expression was associated with time to progression. This study suggests that microRNA expression can be used as biomarkers for clinical course.