Master Regulators of Oncogenic Response in Pancreatic Cancer: An Integrative Network Biology Analysis

1. CRUK. Pancreatic Cancer Risks and Causes 2014. http://www.cancerresearchuk.org/about-cancer/type/pancreatic-cancer/about/pancreatic-cancer-risks-and-causes.

2. Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, Stebbings LA, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010;467(7319):1109–13. doi: 10.1038/nature09460 20981101

3. Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 1988;16(16):7773–82. 3047672

4. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008;321(5897):1801–6. doi: 10.1126/science.1164368 18772397

5. Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature. 2015;518(7540):495–501. doi: 10.1038/nature14169 25719666

6. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012;491(7424):399–405. doi: 10.1038/nature11547 23103869

7. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47(10):1168–78. doi: 10.1038/ng.3398 26343385

8. Collisson EA, Sadanandam A, Olson P, Gibb WJ, Truitt M, Gu S, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med. 2011;17(4):500–3. doi: 10.1038/nm.2344 21460848

9. Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531(7592):47–52. doi: 10.1038/nature16965 26909576

10. Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4(6):437–50. 14706336

11. Collins MA, Bednar F, Zhang Y, Brisset JC, Galban S, Galban CJ, et al. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest. 2012;122(2):639–53. doi: 10.1172/JCI59227 22232209

12. di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 2013;144(6):1220–9. doi: 10.1053/j.gastro.2013.01.071 23622131

13. Castro MA, de Santiago I, Campbell TM, Vaughn C, Hickey TE, Ross E, et al. Regulators of genetic risk of breast cancer identified by integrative network analysis. Nat Genet. 2016;48(1):12–21. doi: 10.1038/ng.3458 26618344

14. Fletcher MN, Castro MA, Wang X, de Santiago I, O'Reilly M, Chin SF, et al. Master regulators of FGFR2 signalling and breast cancer risk. Nat Commun. 2013;4:2464. doi: 10.1038/ncomms3464 24043118

15. Basso K, Margolin AA, Stolovitzky G, Klein U, Dalla-Favera R, Califano A. Reverse engineering of regulatory networks in human B cells. Nat Genet. 2005;37(4):382–90. doi: 10.1038/ng1532 15778709

16. Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Dalla Favera R, et al. ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics. 2006;7 Suppl 1:S7.

17. Schreiber FS, Deramaudt TB, Brunner TB, Boretti MI, Gooch KJ, Stoffers DA, et al. Successful growth and characterization of mouse pancreatic ductal cells: functional properties of the Ki-RAS(G12V) oncogene. Gastroenterology. 2004;127(1):250–60. 15236190

18. Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, et al. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature. 2001;410(6832):1111–6. doi: 10.1038/35074129 11323676

19. Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 2001;15(24):3243–8. doi: 10.1101/gad.943001 11751630

20. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi: 10.1093/nar/gkv007 25605792

21. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):pl1. doi: 10.1126/scisignal.2004088 23550210

22. Gautier L, Cope L, Bolstad BM, Irizarry RA. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307–15. doi: 10.1093/bioinformatics/btg405 14960456

23. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003;4(2):249–64. doi: 10.1093/biostatistics/4.2.249 12925520

24. Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118–27. doi: 10.1093/biostatistics/kxj037 16632515

25. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010;11(10):R106. doi: 10.1186/gb-2010-11-10-r106 20979621

26. Schafer J, Strimmer K. A shrinkage approach to large-scale covariance matrix estimation and implications for functional genomics. Stat Appl Genet Mol Biol. 2005;4:Article32. doi: 10.2202/1544-6115.1175 16646851

27. Strimmer K. fdrtool: a versatile R package for estimating local and tail area-based false discovery rates. Bioinformatics. 2008;24(12):1461–2. doi: 10.1093/bioinformatics/btn209 18441000

28. Stouffer SA, Suchman Edward A., DeVinney Leland C., Star Shirley A., and Williams Robin M. Jr. Studies in Social Psychology in World War II: The American Soldier. Vol. 1, Adjustment During Army Life. Princeton: Princeton University Press.; 1949.

29. Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, et al. Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nat Genet. 2016;48(8):838–47. doi: 10.1038/ng.3593 27322546

30. Clauset A, Newman ME, Moore C. Finding community structure in very large networks. Phys Rev E Stat Nonlin Soft Matter Phys. 2004;70(6 Pt 2):066111. doi: 10.1103/PhysRevE.70.066111 15697438

31. Cingolani P, Platts A, Wang le L, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012;6(2):80–92.

32. Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612. doi: 10.1038/ncomms3612 24113773

33. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27(12):1739–40. doi: 10.1093/bioinformatics/btr260 21546393

34. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7. doi: 10.1038/nmeth.3337 25822800

35. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011;475(7354):106–9. doi: 10.1038/nature10189 21734707

36. Badea L, Herlea V, Dima SO, Dumitrascu T, Popescu I. Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia. Hepatogastroenterology. 2008;55(88):2016–27. 19260470

37. Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, et al. FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell. 2009;16(3):259–66. doi: 10.1016/j.ccr.2009.07.016 19732725

38. Donahue TR, Tran LM, Hill R, Li Y, Kovochich A, Calvopina JH, et al. Integrative survival-based molecular profiling of human pancreatic cancer. Clin Cancer Res. 2012;18(5):1352–63. doi: 10.1158/1078-0432.CCR-11-1539 22261810

39. International Genomics Consortium’s (IGC) Expression Project for Oncology (expO). https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2109

40. The Cancer Genome Atlas Data Portal 2015. http://cancergenome.nih.gov.

41. Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735–47. doi: 10.1016/j.ccr.2014.04.021 24856585

42. Lee JJ, Perera RM, Wang H, Wu DC, Liu XS, Han S, et al. Stromal response to Hedgehog signaling restrains pancreatic cancer progression. Proc Natl Acad Sci U S A. 2014;111(30):E3091–100. doi: 10.1073/pnas.1411679111 25024225

43. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603–7. doi: 10.1038/nature11003 22460905

44. Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov. 2015;14(8):561–84. doi: 10.1038/nrd4591 26228759