title: Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.
abstract: BACKGROUND
  Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer.
  
  
  METHODS
  In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy.
  
  
  RESULTS
  Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences.
  
  
  CONCLUSIONS
  Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer.
authors: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors: Punit
authors: P
authors: Saraon
authors: Dominique
authors: D
authors: Trudel
authors: Ken
authors: K
authors: Kron
authors: Apostolos
authors: A
authors: Dmitromanolakis
authors: John
authors: J
authors: Trachtenberg
authors: Bharati
authors: B
authors: Bapat
authors: Theodorus
authors: T
authors: van der Kwast
authors: Keith A
authors: KA
authors: Jarvi
authors: Eleftherios P
authors: EP
authors: Diamandis
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase
keywords: ACAT1; ketogenesis; progression; prostate cancer