Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer

Eur Urol. 2016 Oct;70(4):549-552. doi: 10.1016/j.eururo.2015.12.003. Epub 2015 Dec 24.

Abstract

The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression.

Patient summary: We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.

Keywords: In situ hybridization; Lethal prostate cancer; Metastatic prostate cancer; SChLAP1; long noncoding RNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / secondary
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • PTEN Phosphohydrolase / metabolism
  • Prostatectomy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • SChLAP1 long noncoding RNA
  • PTEN Phosphohydrolase
  • PTEN protein, human