title: Systems biology approach to identification of biomarkers for metastatic progression in cancer.
abstract: BACKGROUND
  Metastases are responsible for the majority of cancer fatalities. The molecular mechanisms governing metastasis are poorly understood, hindering early diagnosis and treatment. Previous studies of gene expression patterns in metastasis have concentrated on selection of a small number of "signature" biomarkers.
  
  
  RESULTS
  We propose an alternative approach that puts into focus gene interaction networks and molecular pathways rather than separate genes. We have reanalyzed expression data from a large set of primary solid and metastatic tumors originating from different tissues using the latest available tools for normalization, identification of differentially expressed genes and pathway analysis. Our studies indicate that regardless of the tissue of origin, all metastatic tumors share a number of common features related to changes in basic energy metabolism, cell adhesion/cytoskeleton remodeling, antigen presentation and cell cycle regulation. Analysis of multiple independent datasets indicates significantly reduced oxidative phosphorylation in metastases compared to primary solid tumors.
  
  
  CONCLUSIONS
  Our methods allow identification of robust, although not necessarily highly expressed biomarkers. A systems approach relying on groups of interacting genes rather than single markers is also essential for understanding the cellular processes leading to metastatic progression. We have identified metabolic pathways associated with metastasis that may serve as novel targets for therapeutic intervention.
authors.affiliation: Center for Bioinformatics, Department of Microbiology, Immunology and Pathology, Colorado State University, Colorado, USA. Andrey.Ptitsyn@colostate.edu
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Ptitsyn
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weil
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Thamm
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D003198:Computer Simulation; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D010363:Pattern Recognition, Automated / Q000379:methods; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
references.citation: Cancer Treat Rev. 2008 May;34(3):206-22
references.pmid: 18226465
references.citation: Cancer Chemother Pharmacol. 2008 Nov;62(6):985-94
references.pmid: 18253734
references.citation: Cancer Res. 2002 Aug 1;62(15):4499-506
references.pmid: 12154061
references.citation: Chin Med J (Engl). 2007 Dec 20;120(24):2304-7
references.pmid: 18167222
references.citation: Cancer Res. 2005 Mar 15;65(6):2406-11
references.pmid: 15781656
references.citation: Oncol Rep. 2008 Jan;19(1):245-51
references.pmid: 18097602
references.citation: Arch Surg. 2005 Dec;140(12):1184-90
references.pmid: 16365240
references.citation: Bioinformatics. 2005 May 1;21(9):1943-9
references.pmid: 15647293
references.citation: Carcinogenesis. 2006 Jul;27(7):1323-33
references.pmid: 16531451
references.citation: Clin Cancer Res. 2005 Sep 1;11(17):6198-204
references.pmid: 16144921
references.citation: Urology. 2000 Mar;55(3):323-7
references.pmid: 10699601
references.citation: Nat Med. 2004 Feb;10(2):182-6
references.pmid: 14704791
references.citation: Clin Cancer Res. 2003 Jul;9(7):2632-41
references.pmid: 12855641
references.citation: Int J Gynecol Pathol. 2006 Apr;25(2):121-30
references.pmid: 16633060
references.citation: Trends Genet. 2006 Oct;22(10):555-61
references.pmid: 16889869
references.citation: Nat Genet. 2003 Jan;33(1):49-54
references.pmid: 12469122
references.citation: Nature. 2002 Jan 31;415(6871):530-6
references.pmid: 11823860
references.citation: Nat Rev Cancer. 2003 Jun;3(6):453-8
references.pmid: 12778135
references.citation: J Biol Chem. 2006 Aug 25;281(34):24279-92
references.pmid: 16798740
references.citation: J Mammary Gland Biol Neoplasia. 2005 Oct;10(4):291-8
references.pmid: 16900393
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1717-21
references.pmid: 15533898
references.citation: Mol Cancer Ther. 2007 Aug;6(8):2249-60
references.pmid: 17699722
references.citation: J Biol Chem. 2000 Mar 10;275(10):7087-94
references.pmid: 10702275
references.citation: Methods Mol Biol. 2003;224:149-57
references.pmid: 12710672
references.citation: Mol Cell Biol. 2000 May;20(10):3590-6
references.pmid: 10779348
references.citation: Carcinogenesis. 2004 Jul;25(7):1157-63
references.pmid: 14963017
references.citation: J Natl Cancer Inst. 1995 Nov 1;87(21):1588-92
references.pmid: 7563201
references.citation: Nat Rev Cancer. 2006 Feb;6(2):141-6
references.pmid: 16491073
references.citation: Chemotherapy. 2007;53(4):233-56
references.pmid: 17595539
references.citation: Cancer Biol Ther. 2003 Jan-Feb;2(1):14-21
references.pmid: 12673112
references.citation: Genomics. 2003 Feb;81(2):98-104
references.pmid: 12620386
references.citation: Clin Exp Metastasis. 2008;25(4):289-304
references.pmid: 18324357
references.citation: Cancer Res. 2002 Nov 15;62(22):6674-81
references.pmid: 12438266
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Science. 1977 Aug 26;197(4306):893-5
references.pmid: 887927
references.citation: Immunology. 2008 Feb;123(2):218-27
references.pmid: 17725605
references.citation: J Surg Oncol. 2007 Oct 1;96(5):419-23
references.pmid: 17874463
references.citation: J Gastroenterol Hepatol. 2007 Nov;22(11):1916-20
references.pmid: 17914970
references.citation: Bioinformatics. 2006 Oct 15;22(20):2500-6
references.pmid: 16895928
references.citation: Science. 1956 Aug 10;124(3215):269-70
references.pmid: 13351639
references.citation: Genome Biol. 2007;8(9):R183
references.pmid: 17784955
references.citation: Cancer Immunol Immunother. 2008 May;57(5):647-54
references.pmid: 18046553
references.citation: N Engl J Med. 2007 Jan 18;356(3):217-26
references.pmid: 17229949
references.citation: In Vivo. 2002 Nov-Dec;16(6):423-9
references.pmid: 12494885
references.citation: Bioinformatics. 2003 Jan 22;19(2):185-93
references.pmid: 12538238
references.citation: Dig Dis Sci. 2008 Feb;53(2):467-73
references.pmid: 17597401
references.citation: Oncogene. 2002 Nov 7;21(51):7839-49
references.pmid: 12420221
references.citation: Cancer. 2008 May 1;112(9):2088-100
references.pmid: 18327819
references.citation: Zhonghua Zhong Liu Za Zhi. 2007 Sep;29(9):685-8
references.pmid: 18246799
references.citation: Environ Health Perspect. 2003 Nov;111(15):1819-26
references.pmid: 14630514
references.citation: Oncol Rep. 2007 Jun;17(6):1541-9
references.pmid: 17487416
references.citation: J Transl Med. 2007 Dec 10;5:64
references.pmid: 18070359
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Appl Bioinformatics. 2004;3(1):49-62
references.pmid: 16323966