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

Author(s)

Santos, Nilton Jose ^{[1, 2]} ; Barquilha, Caroline Nascimento ^{[1, 2]} ; Barbosa, Isabela Correa ^{[1, 2]} ; Macedo, Rodrigo Tavares ^[3] ; Lima, Flavio Oliveira ^[3] ; Justulin, Luis Antonio ^[1] ; Barbosa, Guilherme Oliveira ^[2] ; Carvalho, Hernandes F. ^[2] ; Felisbino, Sergio Luis ^[1]

Affiliation

^[1] Sao Paulo State Univ, Inst Biosci Botucatu IBB, Dept Struct & Funct Biol, BR-18618689 Botucatu, SP - Brazil

^[2] UNICAMP State Univ Campinas, Inst Biol IB, Dept Struct & Funct Biol, BR-13083970 Campinas, SP - Brazil

^[3] Sao Paulo State Univ, Botucatu Sch Med FMB, BR-01049010 Botucatu, SP - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 16 AUG 2021.
• Web of Science Citations: 0

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 Sdc1 in Pb-Cre4/Pten(f/f) mouse Pca and upregulation of Sdc3 expression and downregulation of Sdc2 and Sdc4 when compared to the normal prostatic tissue in Pb-Cre4/Trp53(f/f)-;Rb1(f/f) 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, p = 0.0047). Analysis of the MSKCC-derived expression showed that SDC1 and SDC3 overexpression is predictive of decreased biochemical recurrence-free survival (p = 0.0099 and p = 0.045, respectively), and SDC4 overexpression is predictive of increased biochemical recurrence-free survival (p = 0.035). SDC4 overexpression was associated with a better prognosis, while SDC1 and SDC3 were associated with more aggressive tumors and a worse prognosis. (AU)

• FAPESP's process: 16/09532-3 - Prostate cancer: changes in the Syndecan proteoglycans, oxidative stress enzyme sulfiredoxin and cell cycle kinase MELK
• Grantee: Sérgio Luis Felisbino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/19644-1 - Prostate cancer: involvement of adiponectin and type X collagen pathways
• Grantee: Sérgio Luis Felisbino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/26175-7 - Stromal alterations in prostate cancer: a study on Syndecan proteoglycans family in two knockout mouse model - PTEN-/- e Rb1-/- Trp53-/-
• Grantee: Nilton José dos Santos
• Support Opportunities: Scholarships in Brazil - Master