title: Expression of SOCS1 and the downstream targets of its putative tumor suppressor functions in prostate cancer.
abstract: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21CIP1(p21). Here, we studied the expression of SOCS1 and the downstream targets of its putative tumor suppressor functions (p53, MET and p21) in human PCa specimens to evaluate their significance as markers of disease prognosis.
  
  
  
  Tissue microarrays were constructed of 78 archived prostatectomy specimens that were grouped according to the recommendations of the International Society of Urological Pathology (ISUP) based on the Gleason patterns. SOCS1, p53, MET and p21 protein expression were evaluated by immunohistochemical staining alongside the common prostate cancer-related markers Ki67, prostein and androgen receptor. Statistical correlations between the staining intensities of these markers and ISUP grade groups, local invasion or lymph node metastasis were evaluated.
  
  
  
  SOCS1 showed diffuse staining in the prostatic epithelium. SOCS1 staining intensity correlated inversely with the ISUP grade groups (ρ = -0.4687, p <0.0001) and Ki67 (ρ = -0.2444, p = 0.031), and positively with prostein (ρ = 0.3511, p = 0.0016). Changes in SOCS1 levels did not significantly associate with those of p53, MET or p21. However, p21 positively correlated with androgen receptor expression (ρ = -0.1388, p = 0.0003). A subset of patients with regional lymph node metastasis, although small in number, showed reduced SOCS1 expression and increased expression of MET and p21.
  
  
  
  Our findings suggest that evaluating SOCS1 and p21 protein expression in prostatectomy specimens may have a prognostic value in identifying the aggressive disease. Hence, prospective studies with larger numbers of metastatic PCa specimens incorporating clinical correlates such as disease-free and overall survival are warranted.
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Chevrier
authors.affiliation: Department of Pediatrics, Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Bobbala
authors.affiliation: Department of Pediatrics, Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villalobos-Hernandez
authors.affiliation: Department of Pediatrics, Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Md Gulam Musawwir
authors.initials: MG
authors.lastname: Khan
authors.affiliation: Department of Pediatrics, Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.|Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS), Sherbrooke, Québec, J1H 5 N4, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.|Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS), Sherbrooke, Québec, J1H 5 N4, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Saucier
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Université de Montréal, Montréal, Canada.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferbeyre
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada.|Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS), Sherbrooke, Québec, J1H 5 N4, Canada.
authors.forename: Sameh
authors.initials: S
authors.lastname: Geha
authors.affiliation: Department of Pediatrics, Immunology division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada. Subburaj.Ilangumaran@USherbrooke.ca.|Centre de recherche du Centre hospitalier universitaire de Sherbrooke (CRCHUS), Sherbrooke, Québec, J1H 5 N4, Canada. Subburaj.Ilangumaran@USherbrooke.ca.
authors.forename: Subburaj
authors.identifier: 0000-0002-7563-576X
authors.initials: S
authors.lastname: Ilangumaran
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein
keywords: MET; Prostate cancer; SOCS1; Tumor suppressor; p21