title: Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer.
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.
  
  
  
  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.
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA. Electronic address: mrohit@med.umich.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Ahearn
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Petimar
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA. Electronic address: arul@med.umich.edu.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C000613525:SChLAP1 long noncoding RNA; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: In situ hybridization; Lethal prostate cancer; Metastatic prostate cancer; SChLAP1; long noncoding RNA