Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression

C. A. DeRosa, B. Furusato, S. Shaheduzzaman, V. Srikantan, Z. Wang, Y. Chen, M. Siefert, L. Ravindranath, D. Young, M. Nau, A. Dobi, T. Werner, D. G. McLeod, M. T. Vahey, I. A. Sesterhenn, S. Srivastava, G. Petrovics*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish
Pages (from-to)150-156
Number of pages7
JournalProstate Cancer and Prostatic Diseases
Issue number2
StatePublished - Jun 2012
Externally publishedYes


  • Gene expression
  • Metastasis
  • Osteonectin/SPARC
  • Prognostic marker


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