Coexpression analysis of large cancer datasets provides insight into the cellular phenotypes of the tumour microenvironment

BMC Genomics

Volumn 14, Issue 1, 2013, Pages

  Doig, Tamasin N ^a,c   Hume, David A ^c   Theocharidis, Thanasis ^c   Goodlad, John R ^b   Gregory, Christopher D ^a   Freeman, Tom C ^c  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b WESTERN GENERAL HOSPITAL   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Cancer; Clustering; Coexpression; Disease networks; Gene signatures; Modules; Stroma; Transcriptomics

Indexed keywords

ARTICLE; BREAST CARCINOMA; CELL INTERACTION; CELL POPULATION; CELL TYPE; COLORECTAL CARCINOMA; COMPUTER PROGRAM; CORRELATION ANALYSIS; GENE CLUSTER; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE IDENTIFICATION; GENETIC ANALYSIS; GENETIC CONSERVATION; GENETIC DATABASE; GERM CELL TUMOR; GLIOMA; HOUSEKEEPING GENE; HUMAN; LARGE CELL LYMPHOMA; MACROPHAGE; MICROARRAY ANALYSIS; MITOSIS INDEX; ONCOGENE; OVARY CARCINOMA; PHENOTYPE; STROMA CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR CELL; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION;

COMPUTER GRAPHICS; CONSERVED SEQUENCE; DATABASES, GENETIC; GENE EXPRESSION PROFILING; GENES, NEOPLASM; HUMANS; NEOPLASMS; PHENOTYPE; TRANSCRIPTION, GENETIC; TUMOR MICROENVIRONMENT;

EID: 84880014085     PISSN: None     EISSN: 14712164     Source Type: Journal    
DOI: 10.1186/1471-2164-14-469     Document Type: Article

References (75)

1. Gordon GJ, Rockwell GN, Jensen RV, Rheinwald JG, Glickman JN, Aronson JP, Pottorf BJ, Nitz MD, Richards WG, Sugarbaker DJ, et al. Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling. AmJPathol 2005, 166(6):1827-1840.
2. Lenburg ME, Liou LS, Gerry NP, Frampton GM, Cohen HT, Christman MF. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data. BMCCancer 2003, 3:31.
3. Linderoth J, Eden P, Ehinger M, Valcich J, Jerkeman M, Bendahl PO, Berglund M, Enblad G, Erlanson M, Roos G, et al. Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma. BrJHaematol 2008, 141(4):423-432.
4. Pawitan Y, Bjohle J, Amler L, Borg AL, Egyhazi S, Hall P, Han X, Holmberg L, Huang F, Klaar S, et al. Gene expression profiling spares early breast cancer patients from adjuvant therapy: derived and validated in two population-based cohorts. Breast Cancer Res 2005, 7(6):R953-R964. 10.1186/bcr1325, 1410752, 16280042.
5. Raponi M, Zhang Y, Yu J, Chen G, Lee G, Taylor JM, Macdonald J, Thomas D, Moskaluk C, Wang Y, et al. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res 2006, 66(15):7466-7472. 10.1158/0008-5472.CAN-06-1191, 16885343.
6. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403(6769):503-511. 10.1038/35000501, 10676951.
7. Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, Joshi MB, Harpole D, Lancaster JM, Berchuck A, et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature 2006, 439(7074):353-357. 10.1038/nature04296, 16273092.
8. Iwamoto T, Pusztai L. Predicting prognosis of breast cancer with gene signatures: are we lost in a sea of data?. Genome Med 2010, 2(11):81. 10.1186/gm202, 3016623, 21092148.
9. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. ProcNatlAcadSciUSA 2004, 101(25):9309-9314.
10. Segal E, Friedman N, Koller D, Regev A. A module map showing conditional activity of expression modules in cancer. NatGenet 2004, 36(10):1090-1098.
11. Shaffer AL, Wright G, Yang L, Powell J, Ngo V, Lamy L, Lam LT, Davis RE, Staudt LM. A library of gene expression signatures to illuminate normal and pathological lymphoid biology. ImmunolRev 2006, 210:67-85.
12. Chuang CL, Jen CH, Chen CM, Shieh GS. A pattern recognition approach to infer time-lagged genetic interactions. Bioinformatics 2008, 24(9):1183-1190. 10.1093/bioinformatics/btn098, 18337258.
13. Stuart JM, Segal E, Koller D, Kim SK. A gene-coexpression network for global discovery of conserved genetic modules. Science 2003, 302(5643):249-255. 10.1126/science.1087447, 12934013.
14. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol 2005, 4. Article17.
15. Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. NatRevCancer 2010, 10(1):2-3.
16. Coffelt SB, Hughes R, Lewis CE. Tumor-associated macrophages: effectors of angiogenesis and tumor progression. BiochimBiophysActa 2009, 1796(1):11-18.
17. Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. NatRevCancer 2008, 8(8):618-631.
18. Buttery RC, Rintoul RC, Sethi T. Small cell lung cancer: the importance of the extracellular matrix. IntJBiochemCell Biol 2004, 36(7):1154-1160.
19. Mantovani A, Sica A, Allavena P, Garlanda C, Locati M. Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. HumImmunol 2009, 70(5):325-330.
20. Myhre S, Mohammed H, Tramm T, Alsner J, Finak G, Park M, Overgaard J, Borresen-Dale AL, Frigessi A, Sorlie T. In silico ascription of gene expression differences to tumor and stromal cells in a model to study impact on breast cancer outcome. PLoS One 2010, 5(11):e14002. 10.1371/journal.pone.0014002, 2988804, 21124964.
21. Freeman TC, Goldovsky L, Brosch M, Van Dongen S, Maziere P, Grocock RJ, Freilich S, Thornton J, Enright AJ. Construction, visualisation, and clustering of transcription networks from microarray expression data. PLoS Comput Biol 2007, 3(10):2032-2042. 2041979, 17967053.
22. Theocharidis A, Van Dongen S, Enright AJ, Freeman TC. Network Visualisation and Analysis of Gene Expression Data using BioLayout Express3D. Nat Protoc 2009, 4(10):1535-1550. 10.1038/nprot.2009.177, 19798086.
23. Hume DA, Summers KM, Raza S, Baillie JK, Freeman TC. Functional clustering and lineage markers: insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations. Genomics 2010, 95(6):328-338. 10.1016/j.ygeno.2010.03.002, 20211243.
24. Mabbott NA, Kenneth Baillie J, Hume DA, Freeman TC. Meta-analysis of lineage-specific gene expression signatures in mouse leukocyte populations. Immunobiology 2010, 215(9-10):724-736.
25. Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, Downing A, Fairbairn L, Kapetanovic R, Raza S, et al. A gene expression atlas of the domestic pig. BMC Biol 2012, 10:90-111. 10.1186/1741-7007-10-90, 23153189.
26. Natividad A, Freeman TC, Jeffries D, Burton MJ, Mabey DC, Bailey RL, Holland MJ. Human conjunctival transcriptome analysis reveals the prominence of innate defense in Chlamydia trachomatis infection. Infect Immun 2010, 78(11):4895-4911. 10.1128/IAI.00844-10, 2976339, 20823212.
27. Van Dongen S. Graph Clustering by Flow Simulation, PhD Thesis 2000, University of Utrecht, http://igitur-archive.library.uu.nl/dissertations/1895620/full.pdf.
28. Liu SM, Xavier R, Good KL, Chtanova T, Newton R, Sisavanh M, Zimmer S, Deng C, Silva DG, Frost MJ, et al. Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes and genes associated with allergic processes. JAllergy ClinImmunol 2006, 118(2):496-503.
29. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, et al. A gene atlas of the mouse and human protein-encoding transcriptomes. ProcNatlAcadSciUSA 2004, 101(16):6062-6067.
30. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. NatProtoc 2009, 4(1):44-57.
31. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. ProcNatlAcadSciUSA 2005, 102(43):15545-15550.
32. Summers KM, Raza S, Van Nimwegen E, Freeman TC, Hume DA. Co-expression of FBN1 with mesenchyme-specific genes in mouse cell lines: implications for phenotypic variability in Marfan syndrome. Eur J Hum Genet 2010, 18(11):1209-1215. 10.1038/ejhg.2010.91, 2987476, 20551991.
33. Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, Hartley L, Robb L, Grosveld FG, Van Der Wees J, et al. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 2007, 9(2):201-209. 10.1038/ncb1530, 17187062.
34. Eeckhoute J, Keeton EK, Lupien M, Krum SA, Carroll JS, Brown M. Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Cancer Res 2007, 67(13):6477-6483. 10.1158/0008-5472.CAN-07-0746, 17616709.
35. Nakshatri H, Badve S. FOXA1 in breast cancer. ExpertRevMolMed 2009, 11:e8.
36. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010, 463(7277):88-92. 10.1038/nature08638, 2845535, 20054396.
37. Barabasi AL, Gulbahce N, Loscalzo J. Network medicine: a network-based approach to human disease. Nat Rev Genet 2011, 12(1):56-68. 10.1038/nrg2918, 3140052, 21164525.
38. Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, Xi Y, Howell P, Metge B, Samant RS, et al. The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics 2008, 1:13. 10.1186/1755-8794-1-13, 2408576, 18442402.
39. De Vries TJ, Smeets M, De Graaf R, Hou-Jensen K, Brocker EB, Renard N, Eggermont AM, Van Muijen GN, Ruiter DJ. Expression of gp100, MART-1, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group. J Pathol 2001, 193(1):13-20.
40. Steingrimsson E, Copeland NG, Jenkins NA. Melanocytes and the microphthalmia transcription factor network. AnnuRevGenet 2004, 38:365-411.
41. Allavena P, Sica A, Solinas G, Porta C, Mantovani A. The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages. Crit RevOncolHematol 2008, 66(1):1-9.
42. Ghilardi C, Chiorino G, Dossi R, Nagy Z, Giavazzi R, Bani M. Identification of novel vascular markers through gene expression profiling of tumor-derived endothelium. BMCGenomics 2008, 9:201.
43. Herbert JM, Stekel D, Sanderson S, Heath VL, Bicknell R. A novel method of differential gene expression analysis using multiple cDNA libraries applied to the identification of tumour endothelial genes. BMC Genomics 2008, 9:153. 10.1186/1471-2164-9-153, 2346479, 18394197.
44. Huminiecki L, Bicknell R. In silico cloning of novel endothelial-specific genes. Genome Res 2000, 10(11):1796-1806. 10.1101/gr.150700, 310981, 11076864.
45. Wallgard E, Larsson E, He L, Hellstrom M, Armulik A, Nisancioglu MH, Genove G, Lindahl P, Betsholtz C. Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature. ArteriosclerThrombVascBiol 2008, 28(8):1469-1476.
46. Strickland LA, Jubb AM, Hongo JA, Zhong F, Burwick J, Fu L, Frantz GD, Koeppen H. Plasmalemmal vesicle-associated protein (PLVAP) is expressed by tumour endothelium and is upregulated by vascular endothelial growth factor-A (VEGF). J Pathol 2005, 206(4):466-475. 10.1002/path.1805, 15971170.
47. Ooi CH, Ivanova T, Wu J, Lee M, Tan IB, Tao J, Ward L, Koo JH, Gopalakrishnan V, Zhu Y, et al. Oncogenic pathway combinations predict clinical prognosis in gastric cancer. PLoS Genet 2009, 5(10):e1000676. 10.1371/journal.pgen.1000676, 2748685, 19798449.
48. Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med 2010, 362(10):875-885. 10.1056/NEJMoa0905680, 2897174, 20220182.
49. Brohee S, Van Helden J. Evaluation of clustering algorithms for protein-protein interaction networks. BMC Bioinforma 2006, 7:488.
50. Mosca E, Bertoli G, Piscitelli E, Vilardo L, Reinbold RA, Zucchi I, Milanesi L. Identification of functionally related genes using data mining and data integration: a breast cancer case study. BMCBioinformatics 2009, 10(12):S8.
51. Shi Z, Derow CK, Zhang B. Co-expression module analysis reveals biological processes, genomic gain, and regulatory mechanisms associated with breast cancer progression. BMC Syst Biol 2010, 4:74. 10.1186/1752-0509-4-74, 2902438, 20507583.
52. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma 2008, 9:559.
53. Pollard JW. Macrophages define the invasive microenvironment in breast cancer. JLeukocBiol 2008, 84(3):623-630.
54. Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, Rimoldi M, Biswas SK, Allavena P, Mantovani A. Macrophage polarization in tumour progression. SeminCancer Biol 2008, 18(5):349-355.
55. Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 2006, 107(5):2112-2122. 10.1182/blood-2005-01-0428, 16269622.
56. Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, et al. Stromal gene signatures in large-B-cell lymphomas. NEnglJMed 2008, 359(22):2313-2323.
57. Hodkinson PS, Elliott T, Wong WS, Rintoul RC, MacKinnon AC, Haslett C, Sethi T. ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell DeathDiffer 2006, 13(10):1776-1788.
58. Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL, Karin M. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 2009, 457(7225):102-106. 10.1038/nature07623, 2746432, 19122641.
59. Phng LK, Gerhardt H. Angiogenesis: a team effort coordinated by notch. DevCell 2009, 16(2):196-208.
60. Liu H, Kennard S, Lilly B. NOTCH3 expression is induced in mural cells through an autoregulatory loop that requires endothelial-expressed JAGGED1. CircRes 2009, 104(4):466-475.
61. Eerola AK, Soini Y, Paakko P. Tumour infiltrating lymphocytes in relation to tumour angiogenesis, apoptosis and prognosis in patients with large cell lung carcinoma. Lung Cancer 1999, 26(2):73-83. 10.1016/S0169-5002(99)00072-0, 10568678.
62. Lissbrant IF, Stattin P, Wikstrom P, Damber JE, Egevad L, Bergh A. Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 2000, 17(3):445-451.
63. Orre M, Rogers PA. Macrophages and microvessel density in tumors of the ovary. Gynecol Oncol 1999, 73(1):47-50. 10.1006/gyno.1998.5292, 10094879.
64. Sickert D, Aust DE, Langer S, Haupt I, Baretton GB, Dieter P. Characterization of macrophage subpopulations in colon cancer using tissue microarrays. Histopathology 2005, 46(5):515-521. 10.1111/j.1365-2559.2005.02129.x, 15842633.
65. Coffelt SB, Chen YY, Muthana M, Welford AF, Tal AO, Scholz A, Plate KH, Reiss Y, Murdoch C, De Palma M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol 2011, 186(7):4183-4190. 10.4049/jimmunol.1002802, 21368233.
66. Coffelt SB, Tal AO, Scholz A, De Palma M, Patel S, Urbich C, Biswas SK, Murdoch C, Plate KH, Reiss Y, et al. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions. Cancer Res 2010, 70(13):5270-5280. 10.1158/0008-5472.CAN-10-0012, 20530679.
67. Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear ED, Sevier CS, Ding H, Koh JL, Toufighi K, Mostafavi S, et al. The genetic landscape of a cell. Science 2010, 327(5964):425-431. 10.1126/science.1180823, 20093466.
68. Jorissen RN, Lipton L, Gibbs P, Chapman M, Desai J, Jones IT, Yeatman TJ, East P, Tomlinson IP, Verspaget HW, et al. DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers. ClinCancer Res 2008, 14(24):8061-8069.
69. Lenz G, Wright GW, Emre NC, Kohlhammer H, Dave SS, Davis RE, Carty S, Lam LT, Shaffer AL, Xiao W, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. ProcNatlAcadSciUSA 2008, 105(36):13520-13525.
70. Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. ClinCancer Res 2008, 14(16):5198-5208.
71. Korkola JE, Houldsworth J, Chadalavada RS, Olshen AB, Dobrzynski D, Reuter VE, Bosl GJ, Chaganti RS. Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. Cancer Res 2006, 66(2):820-827. 10.1158/0008-5472.CAN-05-2445, 16424014.
72. Kauffmann A, Gentleman R, Huber W. arrayQualityMetrics-a bioconductor package for quality assessment of microarray data. Bioinformatics 2009, 25(3):415-416. 10.1093/bioinformatics/btn647, 2639074, 19106121.
73. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003, 4(2):249-264. 10.1093/biostatistics/4.2.249, 12925520.
74. Fruchterman TM, Rheingold EM. Graph drawing by force directed placement. Softw Exp Pract 1991, 21:1129-1164.
75. Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 2003, 4(5):3.