title: Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue.
abstract: BACKGROUND
  Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients.
  
  
  METHODS
  Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks.
  
  
  RESULTS
  In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients.
  
  
  CONCLUSIONS
  Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.
authors.affiliation: Molecular Oncology Group, Portuguese Institute of Oncology, Ed, Laboratórios-Piso 4, Rua Dr, António Bernardino de Almeida 4200-072, Porto, Portugal. oriebir.r@gmail.com
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Cátia
authors.initials: C
authors.lastname: Monteiro
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Hu
authors.forename: Virgínia
authors.initials: V
authors.lastname: Cunha
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: Avelino
authors.initials: A
authors.lastname: Fraga
authors.forename: Paulo
authors.initials: P
authors.lastname: Príncipe
authors.forename: Carlos
authors.initials: C
authors.lastname: Lobato
authors.forename: Francisco
authors.initials: F
authors.lastname: Lobo
authors.forename: António
authors.initials: A
authors.lastname: Morais
authors.forename: Vitor
authors.initials: V
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Sanches-Magalhães
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Francisco
authors.initials: F
authors.lastname: Pina
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000368:Aged; D015992:Body Mass Index; D000090943:Delta-5 Fatty Acid Desaturase; D018450:Disease Progression; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000150:complications* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome