title: Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas.
abstract: 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.
authors.affiliation: Department of Genetics Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Maria Moksnes
authors.initials: MM
authors.lastname: Bjaanaes
authors.forename: Ann Rita
authors.initials: AR
authors.lastname: Halvorsen
authors.forename: Steinar
authors.initials: S
authors.lastname: Solberg
authors.forename: Lars
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.forename: Francesca
authors.initials: F
authors.lastname: Colombo
authors.forename: Marco
authors.initials: M
authors.lastname: Anderlini
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.forename: Elin
authors.initials: E
authors.lastname: Kure
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Odd Terje
authors.initials: OT
authors.lastname: Brustugun
authors.forename: Aslaug
authors.initials: A
authors.lastname: Helland
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D059467:Transcriptome; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: EGFR; KRAS; lung cancer; microRNA; survival