title: Multi-institutional Analysis Shows that Low PCAT-14 Expression Associates with Poor Outcomes in Prostate Cancer.
abstract: Long noncoding RNAs (lncRNAs) are an emerging class of relatively underexplored oncogenic molecules with biological and clinical significance. Current inadequacies for stratifying patients with aggressive disease presents a strong rationale to systematically identify lncRNAs as clinical predictors in localized prostate cancer.
  
  
  
  To identify RNA biomarkers associated with aggressive prostate cancer.
  
  
  
  Radical prostatectomy microarray and clinical data was obtained from 910 patients in three published institutional cohorts: Mayo Clinic I (N=545, median follow-up 13.8 yr), Mayo Clinic II (N=235, median follow-up 6.7 yr), and Thomas Jefferson University (N=130, median follow-up 9.6 yr).
  
  
  
  The primary clinical endpoint was distant metastasis-free survival. Secondary endpoints include prostate cancer-specific survival and overall survival. Univariate and multivariate Cox regression were used to evaluate the association of lncRNA expression and these endpoints.
  
  
  
  An integrative analysis revealed Prostate Cancer Associated Transcript-14 (PCAT-14) as the most prevalent lncRNA that is aberrantly expressed in prostate cancer patients. Down-regulation of PCAT-14 expression significantly associated with Gleason score and a greater probability of metastatic progression, overall survival, and prostate cancer-specific mortality across multiple independent datasets and ethnicities. Low PCAT-14 expression was implicated with genes involved in biological processes promoting aggressive disease. In-vitro analysis confirmed that low PCAT-14 expression increased migration while overexpressing PCAT-14 reduced cellular growth, migration, and invasion.
  
  
  
  We discovered that androgen-regulated PCAT-14 is overexpressed in prostate cancer, suppresses invasive phenotypes, and lower expression is significantly prognostic for multiple clinical endpoints supporting its significance for predicting metastatic disease that could be used to improve patient management.
  
  
  
  We discovered that aberrant prostate cancer associated transcript-14 expression during prostate cancer progression is prevalent across cancer patients. Prostate cancer associated transcript-14 is also prognostic for metastatic disease and survival highlighting its importance for stratifying patients that could benefit from treatment intensification.
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: White
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA; Beaumont Hospital-Dearborn, Transitional Year Program, Dearborn, MI, USA.
authors.forename: Shuang G
authors.initials: SG
authors.lastname: Zhao
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Rozycki
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ha X
authors.initials: HX
authors.lastname: Dang
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: McFadden
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Abdallah M
authors.initials: AM
authors.lastname: Eteleeb
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Ismael A
authors.initials: IA
authors.lastname: Vergara
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Arbeit
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA; Beaumont Hospital-Dearborn, Transitional Year Program, Dearborn, MI, USA; Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: christophermaher@wustl.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
mesh_terms: D000368:Aged; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; C000626014:long non-coding RNA PCAT-14, human
keywords: Aggressive prostate cancer; Genomics; Long noncoding RNA; Metastases; PCAT-14; PRCAT-104; Transcriptome