title: HOTAIR in relation to epithelial-mesenchymal transition and cancer stem cells in molecular subtypes of endometrial cancer.
abstract: BACKGROUND
  Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)-mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers.
  
  
  METHODS
  The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes - SNAIL and SLUG - and the CSCs marker CD133.
  
  
  RESULTS
  Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes.
  
  
  CONCLUSIONS
  Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.
authors: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk - Poland.
authors: Agata
authors: A
authors: Łuczak
authors: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk - Poland.
authors: Anna
authors: A
authors: Supernat
authors: Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdańsk, Gdańsk - Poland.
authors: Sylwia
authors: S
authors: Łapińska-Szumczyk
authors: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk - Poland.
authors: Daniel
authors: D
authors: Jachimowicz
authors: Department of Pathomorphology, Medical University of Gdańsk, Gdańsk - Poland.
authors: Hanna
authors: H
authors: Majewska
authors: Department of Pathology and Neuropathology, Medical University of Gdańsk, Gdańsk - Poland.
authors: Jacek
authors: J
authors: Gulczyński
authors: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk - Poland.
authors: Anna J
authors: AJ
authors: Żaczek
mesh_terms: D000368:Aged; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding