title: Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.
abstract: The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.
authors.affiliation: Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Syring
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Klümper
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Offermann
authors.affiliation: Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Boehm
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: von Mässenhausen
authors.affiliation: Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Majores
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schindler
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Adler
authors.affiliation: Pathology of the University Hospital of Lübeck and Leibniz Research Center Borstel, Lübeck and Borstel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056892:Mediator Complex / Q000235:genetics*; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D059467:Transcriptome; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D056892:Mediator Complex
keywords: MED8; Mediator complex; Pathology Section; cancer; oncomine; transcriptional profile