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Elevated Secreted Protein, Acidic, and Rich in Cysteine (SPARC) mRNA Expression in Neoplastic Prostate Epithelial Cells Correlates with PSA Recurrence after Radical Prostatectomy
Chad DeRosa1, Yongmei Chen*2, Lakshmi Ravindranath*2, Bungo Furusato*3, Christopher Cook*2, Jennifer Cullen*2, Isabell A. Sesterhenn3, David G McLeod1, Shiv Srivastava*2, Gyorgy Petrovics*2
1Walter Reed Army Medical Center, Washington, DC;2Center for Prostate Disease Research, Rockville, MD;3Armed Forces Institute of Pathology, Washington, DC
Introduction: Comparative gene expression signatures of well/moderately differentiated and poorly differentiated prostate cancer (CaP) cells along with knowledge based gene function and transcriptional regulation analyses highlighted alterations of SPARC, and genes linked to it, in poorly differentiated CaP. SPARC is a secreted glycoprotein that supports the migration of CaP cells to bone and demonstrates increased expression in CaP metastatic foci (mCaP) as well as mCaP cell lines. We hypothesized that quantitative determination of SPARC expression levels in prostate tumor cells may have potential to predict aggressive clinical behavior in newly diagnosed patients.
Methods: One hundred twenty five hormone naïve post radical prostatectomy (RP) patients were studied. Patient-matched benign and neoplastic prostate epithelial cells (250 specimens) were collected with LCM from frozen tissue slides. Gene expression of SPARC (normalized to GAPDH) was measured in each specimen by Taqman quantitative RT-PCR and correlated with clinical-pathological features.
Results: Using Student t-test and ANOVA, higher SPARC mRNA expression was found in patients with overall Gleason sum of 8-9 (N=26, p=0.0061) and with poorly differentiated cells (N=23, p=0.0137). Kaplan-Meier unadjusted survival analysis revealed that patients with the highest SPARC expression across median split groups (p=0.0186) had increased risk of PSA recurrence (mean f/u 46.5 months).
Conclusions: High SPARC expression in malignant prostate cells is associated with an increased risk of PSA recurrence, with poorly differentiated cells, and with overall Gleason sum 8-9 in this patient cohort. Therefore, quantitative determination of SPARC gene expression levels in prostate tumor cells may have prognostic utility.
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