Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer

Abstract

Prostate cancer (PCa) is the leading cause of cancer-associated mortality in men, and new biomarkers are still needed. The expression pattern and protein tissue localization of proteoglycans of the syndecan family (SDC 1-4) and syntenin-1 (SDCBP) were determined in normal and prostatic tumor tissue from two genetically engineered mouse models and human prostate tumors. Studies were validated using SDC 1-4 and SDCBP mRNA levels and patient survival data from The Cancer Genome Atlas and CamCAP databases. RNAseq showed increased expression of <i>Sdc1</i> in <i>Pb-Cre4/Pten^f/f</i> mouse Pca and upregulation of <i>Sdc3</i> expression and downregulation of <i>Sdc2</i> and <i>Sdc4</i> when compared to the normal prostatic tissue in <i>Pb-Cre4/Trp53^f/f-;Rb1^f/f</i> mouse tumors. These changes were confirmed by immunohistochemistry. In human PCa, SDC 1-4 and SDCBP immunostaining showed variable localization. Furthermore, Kaplan-Meier analysis showed that patients expressing SDC3 had shorter prostate-specific survival than those without SDC3 expression (log-rank test, <i>p</i> = 0.0047). Analysis of the MSKCC-derived expression showed that <i>SDC1</i> and <i>SDC3</i> overexpression is predictive of decreased biochemical recurrence-free survival (<i>p</i> = 0.0099 and <i>p</i> = 0.045, respectively), and <i>SDC4</i> overexpression is predictive of increased biochemical recurrence-free survival (<i>p</i> = 0.035). SDC4 overexpression was associated with a better prognosis, while SDC1 and SDC3 were associated with more aggressive tumors and a worse prognosis.