title: Profiling of microRNAs in tumor interstitial fluid of breast tumors - a novel resource to identify biomarkers for prognostic classification and detection of cancer.
abstract: It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266 microRNAs were present at higher level in the TIF samples as compared to normal counterparts. Sixty-one of these microRNAs were present in > 75% of the serum samples and were subsequently tested in a validation set. Seven of the 61 microRNAs were associated with poor survival, while 23 were associated with the presence of immune cells and adipocytes. To our knowledge, these data demonstrate for the first time that profiling of microRNAs in TIF can identify novel biomarkers for the prognostic classification and detection of breast cancer. In addition, the present findings demonstrate that microRNAs may represent the cross-talk that occurs between tumor cells and their surrounding stroma.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Ann Rita
authors.initials: AR
authors.lastname: Halvorsen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.|Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Åslaug
authors.initials: Å
authors.lastname: Helland
authors.affiliation: Danish Cancer Society Research Center, Genome Integrity Unit, Cancer Proteomics Group, Copenhagen, Denmark.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gromov
authors.affiliation: Department of Pathology, Center of Diagnostic Investigations, Copenhagen University Hospital, Denmark.
authors.forename: Vera Timmermans
authors.initials: VT
authors.lastname: Wielenga
authors.affiliation: Department of Pathology, Center of Diagnostic Investigations, Copenhagen University Hospital, Denmark.
authors.forename: Maj-Lis Møller
authors.initials: MM
authors.lastname: Talman
authors.affiliation: Section for Molecular Disease Biology and Sino-Danish Breast Cancer Research Center, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Translational Cancer Research Unit, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brunner
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sandhu
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.|Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Danish Cancer Society Research Center, Genome Integrity Unit, Cancer Proteomics Group, Copenhagen, Denmark.
authors.forename: Irina
authors.initials: I
authors.lastname: Gromova
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Norway.
authors.forename: Vilde D
authors.initials: VD
authors.lastname: Haakensen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm
keywords: biomarker; breast cancer; cross-talk; microRNA; microenvironment; tumor interstitial fluid