title: The C-terminal fragment of prostate-specific antigen, a 2331 Da peptide, as a new urinary pathognomonic biomarker candidate for diagnosing prostate cancer.
abstract: OBJECTIVE
  Prostate cancer (PCa) is one of the most common cancers and leading cause of cancer-related deaths in men. Mass screening has been carried out since the 1990s using prostate-specific antigen (PSA) levels in the serum as a PCa biomarker. However, although PSA is an excellent organ-specific marker, it is not a cancer-specific marker. Therefore, the aim of this study was to discover new biomarkers for the diagnosis of PCa.
  
  
  METHODS
  We focused on urine samples voided following prostate massage (digital rectal examination [DRE]) and conducted a peptidomic analysis of these samples using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS(n)). Urinary biomaterials were concentrated and desalted using CM-Sepharose prior to the following analyses being performed by MALDI-TOF/MS(n): 1) differential analyses of mass spectra; 2) determination of amino acid sequences; and 3) quantitative analyses using a stable isotope-labeled internal standard.
  
  
  RESULTS
  Multivariate analysis of the MALDI-TOF/MS mass spectra of urinary extracts revealed a 2331 Da peptide in urine samples following DRE. This peptide was identified as a C-terminal PSA fragment composed of 19 amino acid residues. Moreover, quantitative analysis of the relationship between isotope-labeled synthetic and intact peptides using MALDI-TOF/MS revealed that this peptide may be a new pathognomonic biomarker candidate that can differentiate PCa patients from non-cancer subjects.
  
  
  CONCLUSIONS
  The results of the present study indicate that the 2331 Da peptide fragment of PSA may become a new pathognomonic biomarker for the diagnosis of PCa. A further large-scale investigation is currently underway to assess the possibility of using this peptide in the early detection of PCa.
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Nakagyou-ku, Kyoto, Japan.
authors.forename: Sadanori
authors.initials: S
authors.lastname: Sekiya
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Terada
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Goto
authors.affiliation: Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Nakagyou-ku, Kyoto, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kajihara
authors.affiliation: Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Nakagyou-ku, Kyoto, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kawabata
authors.affiliation: Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Nakagyou-ku, Kyoto, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Department of Clinical Laboratory, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Ikawa
authors.affiliation: Department of Clinical Laboratory, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Oosaga
authors.affiliation: Department of Clinical Laboratory, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Koichi Tanaka Laboratory of Advanced Science and Technology, Shimadzu Corporation, Nakagyou-ku, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine*; D051517:Digital Rectal Examination; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000652:urine*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000652:urine*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine*; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D017430:Prostate-Specific Antigen