title: Expression screening of cancer/testis genes in prostate cancer identifies NR6A1 as a novel marker of disease progression and aggressiveness.
abstract: BACKGROUND
  Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de-repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti-cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate--NR6A1--was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays.
  
  
  RESULTS
  We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation.
  
  
  CONCLUSIONS
  Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness.
authors.affiliation: Inserm Unité 1085-Irset, Université de Rennes 1, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.forename: Bertrand
authors.initials: B
authors.lastname: Evrard
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: Julie
authors.initials: J
authors.lastname: Godet
authors.forename: Xavier
authors.initials: X
authors.lastname: Cathelineau
authors.forename: François
authors.initials: F
authors.lastname: Guillé
authors.forename: Michael
authors.initials: M
authors.lastname: Primig
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1 / Q000235:genetics* / Q000378:metabolism; D009919:Orchiectomy; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D013737:Testis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C539950:NR6A1 protein, human; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1