title: Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data.
abstract: BACKGROUND
  Cancer is a complex disease, triggered by mutations in multiple genes and pathways. There is a growing interest in the application of systems biology approaches to analyze various types of cancer-related data to understand the overwhelming complexity of changes induced by the disease.
  
  
  RESULTS
  We reconstructed a regulatory module network using gene expression, microRNA expression and a clinical parameter, all measured in lymphoblastoid cell lines derived from patients having aggressive or non-aggressive forms of prostate cancer. Our analysis identified several modules enriched in cell cycle-related genes as well as novel functional categories that might be linked to prostate cancer. Almost one-third of the regulators predicted to control the expression levels of the modules are microRNAs. Several of them have already been characterized as causal in various diseases, including cancer. We also predicted novel microRNAs that have never been associated to this type of tumor. Furthermore, the condition-dependent expression of several modules could be linked to the value of a clinical parameter characterizing the aggressiveness of the prostate cancer. Taken together, our results help to shed light on the consequences of aggressive and non-aggressive forms of prostate cancer.
  
  
  BACKGROUND
  The complete regulatory network is available as an interactive supplementary web site at the following URL: http://bioinformatics.psb.ugent.be/webtools/pronet/.
authors.affiliation: Department of Plant Systems Biology, VIB, Ghent University, Gent, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Bonnet
authors.forename: Tom
authors.initials: T
authors.lastname: Michoel
authors.forename: Yves
authors.initials: Y
authors.lastname: Van de Peer
mesh_terms: D000368:Aged; D000465:Algorithms; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D049490:Systems Biology
chemical_list: D035683:MicroRNAs
references.citation: Biosystems. 2006 Feb-Mar;83(2-3):81-90
references.pmid: 16426740
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11755-60
references.pmid: 15284443
references.citation: Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2014-24
references.pmid: 16609010
references.citation: Nat Rev Genet. 2004 Feb;5(2):101-13
references.pmid: 14735121
references.citation: BMC Syst Biol. 2009 May 07;3:49
references.pmid: 19422680
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: PLoS One. 2010 Apr 14;5(4):e10162
references.pmid: 20418949
references.citation: Science. 2004 Oct 22;306(5696):640-3
references.pmid: 15499008
references.citation: Nat Rev Genet. 2009 Feb;10(2):77-82
references.pmid: 19104501
references.citation: Biochemistry. 2004 Jun 8;43(22):7215-25
references.pmid: 15170359
references.citation: Nature. 1999 Dec 2;402(6761 Suppl):C47-52
references.pmid: 10591225
references.citation: BMJ. 2002 Oct 5;325(7367):740
references.pmid: 12364300
references.citation: Clin Cancer Res. 2009 Apr 1;15(7):2281-90
references.pmid: 19318487
references.citation: Nat Rev Cancer. 2004 Jan;4(1):71-8
references.pmid: 14708027
references.citation: J Cell Physiol. 2007 Feb;210(2):370-7
references.pmid: 17111382
references.citation: Cancer Gene Ther. 2009 Mar;16(3):206-16
references.pmid: 18949015
references.citation: Nat Cell Biol. 2005 Feb;7(2):126-36
references.pmid: 15654331
references.citation: Cancer Res. 2009 Apr 15;69(8):3356-63
references.pmid: 19351832
references.citation: J Biol Chem. 2007 Aug 10;282(32):23716-24
references.pmid: 17569667
references.citation: Nat Med. 2004 Aug;10(8):789-99
references.pmid: 15286780
references.citation: Nat Genet. 2003 Jun;34(2):166-76
references.pmid: 12740579
references.citation: Mol Biosyst. 2009 Dec;5(12):1817-30
references.pmid: 19763340
references.citation: Bioinformatics. 2009 Feb 15;25(4):490-6
references.pmid: 19136553
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D98-104
references.pmid: 18927107
references.citation: Bioinformatics. 2005 Aug 15;21(16):3448-9
references.pmid: 15972284
references.citation: Bioinformatics. 2007 Jul 15;23(14):1846-7
references.pmid: 17496320
references.citation: BMC Bioinformatics. 2007 May 03;8 Suppl 2:S5
references.pmid: 17493254
references.citation: Oncogene. 2005 Nov 10;24(49):7337-45
references.pmid: 16007129
references.citation: Bioinformatics. 2008 Jan 15;24(2):176-83
references.pmid: 18033794
references.citation: PLoS One. 2009 Jun 11;4(6):e5878
references.pmid: 19517021
references.citation: Cancer Res. 2009 Dec 15;69(24):9490-7
references.pmid: 19996289
references.citation: BJU Int. 2002 Jul;90(2):162-73
references.pmid: 12081758
references.citation: Cancer Res. 2006 Feb 1;66(3):1712-20
references.pmid: 16452231
references.citation: Toxicol In Vitro. 2010 Apr;24(3):928-35
references.pmid: 19925859
references.citation: Mol Cancer Ther. 2008 Jul;7(7):2152-9
references.pmid: 18645025
references.citation: Nat Rev Mol Cell Biol. 2002 Jan;3(1):11-20
references.pmid: 11823794
references.citation: Biochem Biophys Res Commun. 2008 Nov 7;376(1):86-90
references.pmid: 18765229