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Open Access Highly Accessed Research article

Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue

Ricardo Ribeiro1234*, Cátia Monteiro14, Victoria Catalán35, Pingzhao Hu6, Virgínia Cunha14, Amaia Rodríguez35, Javier Gómez-Ambrosi35, Avelino Fraga127, Paulo Príncipe7, Carlos Lobato8, Francisco Lobo9, António Morais9, Vitor Silva9, José Sanches-Magalhães9, Jorge Oliveira9, Francisco Pina10, Carlos Lopes2, Rui Medeiros11124 and Gema Frühbeck1235*

Author Affiliations

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

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BMC Medicine 2012, 10:108  doi:10.1186/1741-7015-10-108

Published: 25 September 2012

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.

Keywords:
adipose tissue; gene expression; microarray, obesity; periprostatic; prostate cancer