Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue
1 Molecular Oncology Group, Portuguese Institute of Oncology, Ed. Laboratórios-Piso 4, Rua Dr. António Bernardino de Almeida 4200-072, Porto, Portugal
2 ICBAS, Abel Salazar Biomedical Sciences Institute, University of Porto, Rua de Jorge Viterbo Ferreira nº 228, 4050-313, Porto, Portugal
3 Metabolic Research Laboratory, Clínica Universidad de Navarra, Pío XII 36, 31008, Pamplona, Spain
4 LPCC - Portuguese League Against Cancer (NRNorte), Est. Interior da Circunvalação 6657, 4200-177, Porto, Portugal
5 CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain
6 The Center for Applied Genomics, Hospital for Sick Children, MaRS Centre - East Tower 101 College Street, Room 15-705, Toronto, Ontario, M5G 1L7, Canada
7 Urology Department, Porto Hospital Centre, Largo Prof. Abel Salazar 4099-001, Porto, Portugal
8 Urology Department, D. Pedro V Military Hospital, Av. da Boavista 4150-113, Porto, Portugal
9 Urology Department, Portuguese Institute of Oncology, Rua Dr. António Bernardino de Almeida 4200-072, Porto, Portugal
10 Urology Department, S. João Hospital, Al. Prof. Hernâni Monteiro 4200 - 319, Porto, Portugal
11 CEBIMED, Faculty of Health Sciences of Fernando Pessoa University, 4200-150, Porto, Portugal
12 Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pío XII 36, 31008, Pamplona, Spain
BMC Medicine 2012, 10:108 doi:10.1186/1741-7015-10-108Published: 25 September 2012
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.
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.
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.
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.