Splice variant transcripts of the anterior gradient 2 gene as a marker of prostate cancer

Oncotarget. 2014 Sep 30;5(18):8681-9. doi: 10.18632/oncotarget.2365.

Abstract

Anterior gradient 2 (AGR2) is a gene predominantly expressed in mucus-secreting tissues or in endocrine cells. Its expression is drastically increased in tumors including prostate cancer. Here we investigated whether AGR2 transcript levels can be used as a biomarker to detect prostate cancer (PCa). Using a PCR-based approach, we could show that in addition to the wild-type (AGRwt long and short) transcripts, five other AGR2 splice variants (SV) (referred to as AGR2 SV-C, -E, -F, -G and -H) were present in cancer cell lines. In tissue biopsies, SV-H and AGR2wt (short) distinguished between benign and PCa (p ≤ 0.05 n = 32). In urine exosomes, AGR2 SV-G and SV-H outperformed serum PSA. Receiver operating characteristic (ROC) curves showed the highest discriminatory power of SV-G and SV-H in predicting PCa. AGR2 SV-G and SV-H are potential diagnostic biomarkers for the non-invasive detection of PCa using urine exosomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alternative Splicing*
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Biopsy
  • Cell Line, Tumor
  • Exosomes / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Predictive Value of Tests
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / urine
  • Proteins / genetics*
  • RNA, Messenger / urine
  • ROC Curve

Substances

  • AGR2 protein, human
  • Biomarkers, Tumor
  • Proteins
  • RNA, Messenger
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen