title: The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation.
abstract: BACKGROUND
  The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking.
  
  
  METHODS
  SOX11 expression and clinicopathological data was compared using χ² test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation.
  
  
  RESULTS
  SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11.
  
  
  CONCLUSIONS
  SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.
authors.affiliation: Department of Immunotechnology, Lund University, Lund, Sweden. Sara.Ek@immun.lth.se
authors.forename: Sandra
authors.initials: S
authors.lastname: Sernbo
authors.forename: Elin
authors.initials: E
authors.lastname: Gustavsson
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: Elton
authors.initials: E
authors.lastname: Rexhepaj
authors.forename: Frida
authors.initials: F
authors.lastname: Rydnert
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Carl Ak
authors.initials: CA
authors.lastname: Borrebaeck
authors.forename: Sara
authors.initials: S
authors.lastname: Ek
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors