title: miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers.
abstract: BACKGROUND
  The prognostic value of EGFR mutation in lung cancer patients with brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited. Looking for biomarkers closely related with early tumor changes and brain metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are frequently deregulated in lung cancer. The objective of this study was to investigate whether some miRNAs are related with brain metastasis risk in EGFR-mutant non-small cell lung cancer patients.
  
  
  METHODS
  miRNA quantification was retrospectively performed in formalin-fixed, extracranial paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of advanced non-small cell lung cancer patients. Samples were classified as brain metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC patients without BM). The RNA obtained was preamplified and retro-transcribed, and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the QuantStudio™ 12 K Flex Real-Time PCR system.
  
  
  RESULTS
  miRNA-197 and miRNA-184 showed a significant higher expression in EGFRm-BM+ group than in the control group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a trend toward overexpression in BM group compared with the control group (p = 0.08 and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in expression in BM group according to EGFR mutational status (EGFR wild type vs. EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively).
  
  
  CONCLUSIONS
  miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.
authors.affiliation: Medical Oncology Department, Hospital de Mataró, Carretera de la Cirera, s/n, 08304, Mataró, Barcelona, Spain. jremon@csdm.cat.
authors.forename: J
authors.initials: J
authors.lastname: Remon
authors.affiliation: Laboratorio de Motilidad Digestiva CIBERehd, Hospital de Mataró, Carretera de la Cirera, s/n, 08304, Mataró, Barcelona, Spain. dalvarezbe@csdm.cat.
authors.forename: D
authors.initials: D
authors.lastname: Alvarez-Berdugo
authors.affiliation: Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain. mmajem@santpau.cat.
authors.forename: M
authors.initials: M
authors.lastname: Majem
authors.affiliation: Medical Oncology Department, Institut Català d'Oncologia -Badalona, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera de Canyet s/n, 08916, Badalona, Barcelona, Spain. mmoran@iconcologia.net.
authors.forename: T
authors.initials: T
authors.lastname: Moran
authors.affiliation: Medical Oncology Department, Hospital Clinic de Barcelona, Villarroel 170, 08036, Barcelona, Spain. nreguart@clinic.ub.es.
authors.forename: N
authors.initials: N
authors.lastname: Reguart
authors.affiliation: Medical Oncology Department, Hospital de Mataró, Carretera de la Cirera, s/n, 08304, Mataró, Barcelona, Spain. plianes@csdm.cat.
authors.forename: P
authors.initials: P
authors.lastname: Lianes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000556:secondary; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C534424:MIRN184 microRNA, human; C546085:MIRN197 microRNA, human; D035683:MicroRNAs
keywords: Brain metastasis; EGFR mutant; Lung cancer; miRNA-184; miRNA-197