title: MicroRNA signatures in tumor tissue related to angiogenesis in non-small cell lung cancer.
abstract: BACKGROUND
  Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC.
  
  
  METHODS
  From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well-known angiogenic markers were done.
  
  
  RESULTS
  128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR-106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001).
  
  
  CONCLUSIONS
  Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted.
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromsφ, Norway. tom.donnem@uit.no
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Fenton
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lonvik
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Katrine
authors.initials: K
authors.lastname: Eklo
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.forename: Helge
authors.initials: H
authors.lastname: Stenvold
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; D035683:MicroRNAs