title: Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression.
abstract: BACKGROUND
  The majority of prostate cancers (CaP) are detected in early stages with uncertain prognosis. Therefore, an intensive effort is underway to define early predictive markers of CaP with aggressive progression characteristics.
  
  
  METHODS
  In order to define such prognostic markers, we performed comparative analyses of transcriptomes of well- and poorly differentiated (PD) tumor cells from primary tumors of patients (N=40) with 78 months of mean follow-up after radical prostatectomy. Validation experiments were carried out at transcript level by quantitative real-time reverse transcriptase-PCR (RT-PCR) (N=110) and at protein level by immunohistochemistry (N=53) in primary tumors from an independent patient cohort.
  
  
  RESULTS
  Association of a biochemical network of 12 genes with SPARC gene as a central node was highlighted with PD phenotype. Of note, there was remarkable enrichment of NKXH_NKXH_HOX composite regulatory elements in the promoter of the genes in this network suggesting a biological significance of this gene-expression regulatory mechanism in CaP progression. Further, quantitative expression analyses of SPARC mRNA in primary prostate tumor cells of 110 patients validated the association of SPARC expression with poor differentiation and higher Gleason score. Most significantly, higher SPARC protein expression at the time of prostatectomy was associated with the subsequent development of metastasis (P=0.0006, AUC=0.803).
  
  
  CONCLUSIONS
  In summary, we propose that evaluation of SPARC in primary CaP has potential as a prognostic marker of metastatic progression.
authors.affiliation: Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Rockville, MD 20852, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Derosa
authors.forename: B
authors.initials: B
authors.lastname: Furusato
authors.forename: S
authors.initials: S
authors.lastname: Shaheduzzaman
authors.forename: V
authors.initials: V
authors.lastname: Srikantan
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Seifert
authors.forename: M
authors.initials: M
authors.lastname: Siefert
authors.forename: L
authors.initials: L
authors.lastname: Ravindranath
authors.forename: D
authors.initials: D
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Nau
authors.forename: A
authors.initials: A
authors.lastname: Dobi
authors.forename: T
authors.initials: T
authors.lastname: Werner
authors.forename: D G
authors.initials: DG
authors.lastname: McLeod
authors.forename: M T
authors.initials: MT
authors.lastname: Vahey
authors.forename: I A
authors.initials: IA
authors.lastname: Sesterhenn
authors.forename: S
authors.initials: S
authors.lastname: Srivastava
authors.forename: G
authors.initials: G
authors.lastname: Petrovics
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000556:secondary*; D002454:Cell Differentiation; D018450:Disease Progression; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000096:biosynthesis*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015676:Osteonectin; D012333:RNA, Messenger