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Basic Research

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

Prostate Cancer and Prostatic Diseases volume 15, pages 150–156 (2012)Cite this article

A Corrigendum to this article was published on 20 December 2011

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.

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Acknowledgements

This work was supported by grant RO1-DK065977 to SS and GP from the National Institutes of Health, and by the Center for Prostate Disease Research, a program of the Henry M. Jackson Foundation for the Advancement of Military Medicine (Rockville, MD), funded by the US Army Medical Research and Materiel Command.

Disclaimer

The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense or the US Government.

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Author notes

  1. C A DeRosa

    Present address: 7Current address: Urology Service, William Beaumont Army Medical Center, El Paso, TX 79920, USA.,

Authors and Affiliations

  1. Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Rockville, MD, USA

    C A DeRosa, B Furusato, S Shaheduzzaman, V Srikantan, Y Chen, L Ravindranath, D Young, A Dobi, D G McLeod, S Srivastava & G Petrovics

  2. Urology Service, Walter Reed Army Medical Center, Washington, DC, USA

    C A DeRosa & D G McLeod

  3. Department of Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, DC, USA

    B Furusato & I A Sesterhenn

  4. Walter Reed Army Institute of Research, Silver Spring, MD, USA

    Z Wang, M Nau & M T Vahey

  5. Genomatix GmbH., Munich, Germany

    M Siefert & T Werner

  6. United States Military Cancer Institute, Washington, DC, USA

    A Dobi, D G McLeod & S Srivastava

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Correspondence to S Srivastava or G Petrovics.

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Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

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DeRosa, C., Furusato, B., Shaheduzzaman, S. et al. Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression. Prostate Cancer Prostatic Dis 15, 150–156 (2012). https://doi.org/10.1038/pcan.2011.61

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