title: The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer.
abstract: OBJECTIVE
  Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH) proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry) in human non-small cell lung cancer (NSCLC) samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features.
  
  
  METHODS
  One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables.
  
  
  RESULTS
  The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry) in non-small cell lung cancer (NSCLC). We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC) and squamous cell lung cancer (SCC). Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(18F)fluoro-D-glucose) uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates, the serine/threonine kinase DYRK2.
  
  
  CONCLUSIONS
  Our results provide insight into the potential use of SIAH2 as a novel target for lung cancer treatment.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.|Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Moreno
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Lara-Chica
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Soler-Torronteras
authors.affiliation: Department of Pathology, Hospital Universitario Reina Sofía, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ University of Córdoba, 14004 Córdoba, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Caro
authors.affiliation: Department of Pathology, Hospital Universitario Reina Sofía, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ University of Córdoba, 14004 Córdoba, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Medina
authors.affiliation: Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Álvarez
authors.affiliation: Thoracic Surgery and Lung Transplantation Unit, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Salvatierra
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Spain, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/ Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Calzado
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D001692:Biological Transport; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D000097603:Dyrk Kinases; D000098563:Seven in Absentia Proteins
chemical_list: D019788:Fluorodeoxyglucose F18; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; D000097603:Dyrk Kinases; D000098563:Seven in Absentia Proteins