title: Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: results of a profiling study.
abstract: MicroRNAs (miRNAs) are a class of small (∼22 nucleotides), non-coding, highly conserved single-stranded RNAs with posttranscriptional regulatory features, including the regulation of cell proliferation, differentiation, survival, and apoptosis. They are deregulated in a broad variety of tumors showing characteristic expression patterns and can, thus, be used as a diagnostic tool. In contrast to non-small cell carcinoma of the lung neuroendocrine lung tumors, encompassing typical and atypical carcinoids, small cell lung cancer and large cell neuroendocrine lung cancer, no data about deregulation of tumor entity-specific miRNAs are available to date. miRNA expression differences might give useful information about the biological characteristics of these tumors, as well as serve as helpful markers.In 12 pulmonary neuroendocrine tumors classified as either typical carcinoid, atypical, large cell neuroendocrine or small cell lung cancer, screening for 763 miRNAs known to be involved in pulmonary cancerogenesis was conducted by performing 384-well TaqMan low-density array real-time qPCR. In the entire cohort, 44 miRNAs were identified, which showed a significantly different miRNA expression. For 12 miRNAs, the difference was highly significant (P<0.01). Eight miRNAs showed a negative (miR-22, miR-29a, miR-29b, miR-29c, miR-367*; miR-504, miR-513C, miR-1200) and four miRNAs a positive (miR-18a, miR-15b*, miR-335*, miR-1201) correlation to the grade of tumor biology. The miRNAs let-7d; miR-19; miR-576-5p; miR-340*; miR-1286 are significantly associated with survival. Members of the miR-29 family seem to be extremely important in this group of tumors. We found a number of miRNAs, which showed a highly significant deregulation in pulmonary neuroendocrine tumors. Moreover, some of these deregulated miRNAs seem to allow discrimination of the various subtypes of pulmonary neuroendocrine tumors. Thus, the analysis of specific sets of miRNAs can be proposed as diagnostic and/or predictive markers in this group of neoplasias.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Fabian Dominik
authors.initials: FD
authors.lastname: Mairinger
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Ting
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Werner
authors.affiliation: 1] Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany [2] Department of interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Robert Fred Henry
authors.initials: RF
authors.lastname: Walter
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hager
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vollbrecht
authors.affiliation: Department of Medical Oncology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Christoph
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Worm
authors.affiliation: Department of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mairinger
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sien-Yi
authors.initials: SY
authors.lastname: Sheu-Grabellus
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Theegarten
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D035683:MicroRNAs / Q000032:analysis*; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000401:mortality; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs