Exploring prostate cancer genome reveals simultaneous losses of PTEN, FAS and PAPSS2 in patients with PSA recurrence after radical prostatectomy

Int J Mol Sci. 2015 Feb 11;16(2):3856-69. doi: 10.3390/ijms16023856.

Abstract

The multifocal nature of prostate cancer (PCa) creates a challenge to patients' outcome prediction and their clinical management. An approach that scrutinizes every cancer focus is needed in order to generate a comprehensive evaluation of the disease, and by correlating to patients' clinico-pathological information, specific prognostic biomarker can be identified. Our study utilized the Affymetrix SNP 6.0 Genome-wide assay to investigate forty-three fresh frozen PCa tissue foci from twenty-three patients. With a long clinical follow-up period that ranged from 2.0-9.7 (mean 5.4) years, copy number variation (CNV) data was evaluated for association with patients' PSA status during follow-up. From our results, the loss of unique genes on 10q23.31 and 10q23.2-10q23.31 were identified to be significantly associated to PSA recurrence (p < 0.05). The implication of PTEN and FAS loss (10q23.31) support previous reports due to their critical roles in prostate carcinogenesis. Furthermore, we hypothesize that the PAPSS2 gene (10q23.2-10q23.31) may be functionally relevant in post-operative PSA recurrence because of its reported role in androgen biosynthesis. It is suggestive that the loss of the susceptible region on chromosome 10q, which implicates PTEN, FAS and PAPSS2 may serve as genetic predictors of PSA recurrence after radical prostatectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chromosomes, Human, Pair 10 / genetics
  • DNA Copy Number Variations
  • Gene Deletion
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / genetics*
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase / genetics*
  • Prognosis
  • Prostate-Specific Antigen / analysis*
  • Prostate-Specific Antigen / metabolism
  • Prostatectomy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / surgery
  • Sulfate Adenylyltransferase / genetics*
  • fas Receptor / genetics*

Substances

  • FAS protein, human
  • Multienzyme Complexes
  • fas Receptor
  • PAPS synthetase
  • Sulfate Adenylyltransferase
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Prostate-Specific Antigen