title: Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.
abstract: BACKGROUND
  Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.
  
  
  METHODS
  ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1).
  
  
  CONCLUSIONS
  By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94).
  
  
  CONCLUSIONS
  We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon, CNRS UMR5242, INRA1288, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Dogus Murat
authors.initials: DM
authors.lastname: Altintas
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allioli
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin
authors.forename: Simon
authors.initials: S
authors.lastname: de Bernard
authors.forename: Alain
authors.initials: A
authors.lastname: Ruffion
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Virginie
authors.initials: V
authors.lastname: Vlaeminck-Guillem
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009928:Organ Specificity; D028044:Phosphate-Binding Proteins; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012669:Seminal Vesicles / Q000378:metabolism; D045165:Testosterone Congeners / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C112303:CAVIN2 protein, human; C059215:CRYAB protein, human; D002352:Carrier Proteins; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D028044:Phosphate-Binding Proteins; D012333:RNA, Messenger; D045165:Testosterone Congeners; D014157:Transcription Factors; D038203:alpha-Crystallin B Chain; C479341:prostate cancer antigen 3, human; D015741:Metribolone