title: Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer.
abstract: BACKGROUND
  Early diagnosis of prostate cancer and identification of new prognostic factors remain main issues in prostate cancer research. In this study, we sought to test a panel of cancer-specific markers in urine samples as an aid for early cancer diagnosis.
  
  
  METHODS
  Sedimented urine samples of 66 candidates for needle biopsy were tested. Real time-polymerase chain reaction (RT-PCR) was applied to detect the expression of transmembrane protease serine-2 and Ets-related gene fusion (TMPRSS2-ERG), Ets-related gene (ERG), prostate cancer antigen-3 (PCA3), and serine peptidase inhibitor kazal type-1 (SPINK1) transcripts. For testing of the methylation status of Glutahione S-tranferase P (GSTP1) and Ras association domain family member-1(RASSF1A) promoter region, methylation-specific PCR (MSP-PCR) was applied.
  
  
  RESULTS
  Among the tested parameters, the presence of TMPRSS2-ERG (OR=9.044, 95% CI=2.207-37.066, p=0.002), as well as a positive test result for PCA3 (OR=7.549, 95% CI=1,858-30,672, p=0.005) were associated with the subsequent diagnosis of prostate cancer. A multivariable logistic regression including all the significantly associated variables [prostate-specific antigen (PSA), digital rectal examination (DRE), TMPRSS2-ERG and PCA3], yielded a model with area under the receiver-operating characteristic curve (AUC) =0.894 (95% CI=0.772-1.00).
  
  
  CONCLUSIONS
  A multiplexed quantitative PCR analysis on sedimented urine, in conjunction with the results of serum PSA levels and DRE, has the potential to accurately foresee subsequent needle biopsy outcomes. On the basis of the above, algorithms may be designed to guide decisions for needle biopsy.
authors.affiliation: Department of Genetics, St. Savvas Anticancer Hospital, Alexandras Ave 171, 11522, Athens, Greece. dthimios@hotmail.com
authors.forename: Efthymios
authors.initials: E
authors.lastname: Dimitriadis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kalogeropoulos
authors.forename: Stamatia
authors.initials: S
authors.lastname: Velaeti
authors.forename: Sotirios
authors.initials: S
authors.lastname: Sotiriou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassiliou
authors.forename: Loukas
authors.initials: L
authors.lastname: Fasoulis
authors.forename: Vasilios
authors.initials: V
authors.lastname: Klapsas
authors.forename: Michalis
authors.initials: M
authors.lastname: Synesiou
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Apostolaki
authors.forename: Theoni
authors.initials: T
authors.lastname: Trangas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pandis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine*; D001707:Biopsy, Needle; D002352:Carrier Proteins / Q000235:genetics / Q000652:urine; D019175:DNA Methylation / Q000235:genetics; D051517:Digital Rectal Examination; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic / Q000235:genetics*; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000652:urine; D057089:Pathology, Molecular; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000652:urine; D015534:Trans-Activators / Q000235:genetics / Q000652:urine; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000652:urine
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C411762:RASSF1 protein, human; C486642:SPINK1 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D025521:Tumor Suppressor Proteins; C479341:prostate cancer antigen 3, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017430:Prostate-Specific Antigen