title: Steroid Receptor RNA Activator Protein (SRAP): a potential new prognostic marker for estrogen receptor-positive/node-negative/younger breast cancer patients.
abstract: BACKGROUND
  The steroid receptor RNA activator is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression. This RNA is also able to encode for a protein, Steroid Receptor RNA Activator Protein (SRAP), whose exact function remains to be determined. Our aim was to assess, in a large breast cancer cohort, whether levels of this protein could be associated with outcome or established clinical parameters.
  
  
  METHODS
  Following antibody validation, SRAP expression was assessed by tissue-microarray (TMA) analysis of 372 breast tumors. Clinical follow-up and parameters such as steroid receptor and node status were available for all the corresponding cases. Immunohistochemical scores were independently determined by three investigators and averaged. Statistical analyses were performed using standard univariate and multivariate tests.
  
  
  RESULTS
  SRAP levels were significantly (Mann-Whitney rank sum test, P < 0.05) higher in estrogen receptor-alpha positive (ER+, n = 271), in progesterone receptor positive (PR+, n = 257) and in older patients (age > 64 years, n = 182). When considering ER+ tumors, PR+ tumors, or younger patients (< or = 64 years), cases with high SRAP expression had a significantly (Mantel-Cox test, P < 0.05) worse breast cancer specific survival (BCSS) than those with low SRAP levels. SRAP also appeared as a very powerful indicator of poor prognostic for BCSS in the subset of ER+, node negative and young breast cancer patients (Cox regression analysis, n = 60, BCSS Hazard Ratio = 8.61, P < 0.006).
  
  
  CONCLUSIONS
  Our data suggest that SRAP levels might provide additional information on potential risk of recurrence and negative outcome in a specific set of patients with otherwise good prognosis when considering only estrogen receptor and nodal status.
authors.affiliation: Manitoba Institute of Cell Biology, 675 McDermot Avenue, R3E0V9, Winnipeg, Manitoba, Canada. umyan9@cc.umanitoba.ca
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.forename: George P
authors.initials: GP
authors.lastname: Skliris
authors.forename: Carla
authors.initials: C
authors.lastname: Penner
authors.forename: Shilpa
authors.initials: S
authors.lastname: Chooniedass-Kothari
authors.forename: Charlton
authors.initials: C
authors.lastname: Cooper
authors.forename: Zoann
authors.initials: Z
authors.lastname: Nugent
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Peter H
authors.initials: PH
authors.lastname: Watson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Myal
authors.forename: Leigh C
authors.initials: LC
authors.lastname: Murphy
authors.forename: Etienne
authors.initials: E
authors.lastname: Leygue
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D046228:Microarray Analysis / Q000379:methods; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D011960:Receptors, Estrogen; C405423:steroid receptor RNA activator