title: The dyslexia candidate gene DYX1C1 is a potential marker of poor survival in breast cancer.
abstract: BACKGROUND
  The dyslexia candidate gene, DYX1C1, shown to regulate and interact with estrogen receptors and involved in the regulation of neuronal migration, has recently been proposed as a putative cancer biomarker. This study was undertaken to assess the prognostic value and therapy-predictive potential of DYX1C1 mRNA and protein expression in breast cancer.
  
  
  METHODS
  DYX1C1 mRNA expression was assessed at the mRNA level in three independent population-derived patient cohorts. An association to estrogen/progesterone receptor status, Elston grade, gene expression subtype and lymph node status was analyzed within these cohorts. DYX1C1 protein expression was examined using immunohistochemistry in cancer and normal breast tissue. The statistical analyses were performed using the non-parametric Wilcoxon rank-sum test, ANOVA, Fisher's exact test and a multivariate proportional hazard (Cox) model.
  
  
  RESULTS
  DYX1C1 mRNA is significantly more highly expressed in tumors that have been classified as estrogen receptor α and progesterone receptor-positive. The expression of DYX1C1 among the molecular subtypes shows the lowest median expression within the basal type tumors, which are considered to have the worst prognosis. The expression of DYX1C1 is significantly lower in tumors graded as Elston grade 3 compared with grades 1 and 2. DYX1C1 protein is expressed in 88% of tumors and in all 10 normal breast tissues examined. Positive protein expression was significantly correlated to overall survival (Hazard ratio 3.44 [CI 1.84-6.42]) of the patients but not to any of the variables linked with mRNA expression.
  
  
  CONCLUSIONS
  We show that the expression of DYX1C1 in breast cancer is associated with several clinicopathological parameters and that loss of DYX1C1 correlates with a more aggressive disease, in turn indicating that DYX1C1 is a potential prognostic biomarker in breast cancer.
authors.affiliation: Department of Biosciences and Nutrition, Novum, and Science for Life Laboratory, Karolinska Institutet, Hälsovägen 7, Huddinge, Sweden. gustaf.rosin@ki.se
authors.forename: Gustaf
authors.initials: G
authors.lastname: Rosin
authors.forename: Ulf
authors.initials: U
authors.lastname: Hannelius
authors.forename: Linda
authors.initials: L
authors.lastname: Lindström
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Johan
authors.initials: J
authors.lastname: Hartman
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C478878:DNAAF4 protein, human; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger