Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma

PLoS ONE

Volumn 9, Issue 5, 2014, Pages

  Martin, Jeffrey W ^a   Chilton MacNeill, Susan ^a   Koti, Madhuri ^c   Van Wijnen, Andre J ^b   Squire, Jeremy A ^c,d   Zielenska, Maria ^a  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b MAYO GRADUATE SCHOOL   (United States)

^c QUEEN S UNIVERSITY   (Canada)

^d UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

CISPLATIN; DOXORUBICIN; IFOSFAMIDE; MESSENGER RNA; METHOTREXATE; CDC5L PROTEIN, HUMAN; CDK4 PROTEIN, HUMAN; CELL CYCLE PROTEIN; CYCLIN DEPENDENT KINASE 4; GENETIC MARKER; MDM2 PROTEIN, HUMAN; PROTEIN MDM2; RECQ HELICASE; RECQL4 PROTEIN, HUMAN; RNA BINDING PROTEIN; RUNX2 PROTEIN, HUMAN; TRANSCRIPTION FACTOR RUNX2;

AKT GENE; ARTICLE; AUTOMATION; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CDC5L GENE; CDK4 GENE; CHILDHOOD CANCER; CLINICAL ARTICLE; CONTROLLED STUDY; DIAGNOSTIC TEST ACCURACY STUDY; DRUG RESPONSE; EQUIPMENT DESIGN; FEMALE; GENE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE EXPRESSION SYSTEM; GENE FUNCTION; GENE IDENTIFICATION; GENE REGULATORY NETWORK; GENETIC CORRELATION; GENETIC MARKER; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MDM2 GENE; ONCOGENE MYC; OSTEOSARCOMA; PI3K GENE; PROCESS CONTROL; PROCESS DESIGN; PROCESS DEVELOPMENT; PROCESS OPTIMIZATION; PROCESS TECHNOLOGY; PTEN GENE; RB1 GENE; RECQL4 GENE; RUNX2 GENE; SIGNAL PROCESSING; SIGNAL TRANSDUCTION; SYSTEM ANALYSIS; TP53 GENE; ADJUVANT THERAPY; ADOLESCENT; CHILD; DRUG THERAPY; GENETICS; PROCEDURES; TREATMENT OUTCOME;

ADOLESCENT; CELL CYCLE PROTEINS; CHILD; CORE BINDING FACTOR ALPHA 1 SUBUNIT; CYCLIN-DEPENDENT KINASE 4; DRUG THERAPY; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; GENETIC MARKERS; HUMANS; MALE; NEOADJUVANT THERAPY; OSTEOSARCOMA; PROTO-ONCOGENE PROTEINS C-MDM2; RECQ HELICASES; RNA-BINDING PROTEINS; TREATMENT OUTCOME;

EID: 84901335610     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0095843     Document Type: Article

References (60)

1. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, et al. (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20(3): 776-790. (Pubitemid 34111386)
2. Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH, Romeo S, Oosting J, et al. (2009) Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumorigenic pathways. Br J Cancer 101(11): 1909-1918.
3. Martin JW, Squire JA, Zielenska M (2012) The genetics of osteosarcoma. Sarcoma 2012: 627254.
4. Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF (2011) The molecular pathogenesis of osteosarcoma: a review. Sarcoma 2011: 959248.
5. Selvarajah S, Yoshimoto M, Ludkovski O, Park PC, Bayani J, et al. (2008) Genomic signatures of chromosomal instability and osteosarcoma progression detected by high resolution array CGH and interphase FISH. Cytogenet Genome Res 122(1): 5-15.
6. Chibon F, Lagarde P, Salas S, Perot G, Brouste V, et al. (2010) Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat Med 16(7): 781-787.
7. Helman LJ, Meltzer P (2003) Mechanisms of sarcoma development. Nat Rev Cancer 3(9): 685-694. (Pubitemid 37328823)
8. Scott MC, Sarver AL, Gavin KJ, Thayanithy V, Getzy DM, et al. (2011) Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach. Bone 49(3): 356-367.
9. Lu XY, Lu Y, Zhao YJ, Jaeweon K, Kang J, et al. (2008) Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Mol Cancer Res 6(6): 937-946.
10. Sadikovic B, Thorner P, Chilton-Macneill S, Martin JW, Cervigne NK, et al. (2010) Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy. BMC Cancer 10: 202.
11. Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire JA, et al. (2009) Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet 18(11): 1962-1975.
12. Namlos HM, Kresse SH, Muller CR, Henriksen J, Holdhus R, et al. (2012) Global gene expression profiling of human osteosarcomas reveals metastasis-associated chemokine pattern. Sarcoma 2012: 639038.
13. Northcott PA, Shih DJ, Remke M, Cho YJ, Kool M, et al. (2012) Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol 123(4): 615-626.
14. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, et al. (2008) Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 26(3): 317-325. (Pubitemid 351355126)
15. Nathan SS, Pereira BP, Zhou YF, Gupta A, Dombrowski C, et al. (2009) Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma. Mol Biol Rep 36(1): 153-158.
16. Xiao ZS, Thomas R, Hinson TK, Quarles LD (1998) Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor. Gene 214(1-2): 187-197. (Pubitemid 28359207)
17. Dalla-Torre CA, Yoshimoto M, Lee CH, Joshua AM, de Toledo SR, et al. (2006) Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 6: 237.
18. Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, et al. (1998) C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology 55(6): 556-563. (Pubitemid 28479115)
19. Shimizu T, Ishikawa T, Sugihara E, Kuninaka S, Miyamoto T, et al. (2010) c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis. Oncogene 29(42): 5687-5699.
20. Wang ZX, Yang JS, Pan X, Wang JR, Li J, et al. (2010) Functional and biological analysis of Bcl-xL expression in human osteosarcoma. Bone 47(2): 445-454.
21. Yoshida A, Ushiku T, Motoi T, Beppu Y, Fukayama M, et al. (2012) MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype. Am J Surg Pathol 36(3): 423-431.
22. Feugeas O, Guriec N, Babin-Boilletot A, Marcellin L, Simon P, et al. (1996) Loss of heterozygosity of the RB gene is a poor prognostic factor in patients with osteosarcoma. J Clin Oncol 14(2): 467-472. (Pubitemid 26051009)
23. Freeman SS, Allen SW, Ganti R,Wu J, Ma J, et al. (2008) Copy number gains in EGFR and copy number losses in PTEN are common events in osteosarcoma tumors. Cancer 113(6): 1453-1461.
24. Kurek KC, Del Mare S, Salah Z, Abdeen S, Sadiq H, et al. (2010) Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Res 70(13): 5577-5586.
25. Mohseny AB, Tieken C, van der Velden PA, Szuhai K, de Andrea C, et al. (2010) Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma. Genes Chromosom Cancer 49(12): 1095-1103.
26. Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, et al. (2000) Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet 120(2): 91-98. (Pubitemid 30609685)
27. Wunder JS, Gokgoz N, Parkes R, Bull SB, Eskandarian S, et al. (2005) TP53 mutations and outcome in osteosarcoma: a prospective, multicenter study. J Clin Oncol 23(7): 1483-1490.
28. Lapenna S, Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nature Rev 8(7): 547-566.
29. Janssens N, Janicot M, Perera T, Bakker A (2004) Housekeeping genes as internal standards in cancer research. Mol Diagn 8(2): 107-113. (Pubitemid 39363465)
30. Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, et al. (2009) Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia 11(3): 260-268.
31. Teplyuk NM, Galindo M, Teplyuk VI, Pratap J, Young DW, et al. (2008) RUNX2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. J Biol Chem 283(41): 27585-27597.
32. Kuijjer ML, Rydbeck H, Kresse SH, Buddingh EP, Lid AB, et al. (2012) Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data. Genes Chromosom Cancer 51(7): 696-706.
33. Clark JC, Dass CR, Choong PF (2008) A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol 134(3): 281-297. (Pubitemid 351170066)
34. Malkov VA, Serikawa KA, Balantac N, Watters J, Geiss G, et al. (2009) Multiplexed measurements of gene signatures in different analytes using the Nanostring nCounter Assay System. BMC Res Notes 2: 80.
35. Turner NC, Reis-Filho JS (2012) Genetic heterogeneity and cancer drug resistance. Lancet Oncol 13(4): e178-185.
36. Thangavel S, Mendoza-Maldonado R, Tissino E, Sidorova JM, Yin J, et al. (2010) Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Cell Mol Biol 30(6): 1382-1396.
37. Wang LL, Gannavarapu A, Kozinetz CA, Levy ML, Lewis RA, et al. (2003) Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 95(9): 669-674. (Pubitemid 36603723)
38. Bernstein HS, Coughlin SR (1998) A mammalian homolog of fission yeast Cdc5 regulates G2 progression and mitotic entry. J Biol Chem 273(8): 4666-4671. (Pubitemid 28103213)
39. Zhang N, Kaur R, Akhter S, Legerski RJ (2009) Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. EMBO reports 10(9): 1029-1035.
40. Malumbres M, Barbacid M (2007) Cell cycle kinases in cancer. Curr Opin Genet Dev 17(1): 60-65. (Pubitemid 46109297)
41. Dujardin F, Binh MB, Bouvier C, Gomez-Brouchet A, Larousserie F, et al. (2011) MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibroosseous lesions of the bone. Mod Pathol 24(5): 624-637.
42. Kyriazoglou AI, Vieira J, Dimitriadis E, Arnogiannaki N, Teixeira MR, et al. (2012) 12q amplification defines a subtype of extraskeletal osteosarcoma with good prognosis that is the soft tissue homologue of parosteal osteosarcoma. Cancer Genet 205(6): 332-336.
43. Smida J, Baumhoer D, Rosemann M, Walch A, Bielack S, et al. (2010) Genomic alterations and allelic imbalances are strong prognostic predictors in osteosarcoma. Clin Cancer Res. 16(16): 4256-4267.
44. Won KY, Park HR, Park YK (2009) Prognostic implication of immunohistochemical Runx2 expression in osteosarcoma. Tumori 95(3): 311-316.
45. Lee JS, Thomas DM, Gutierrez G, Carty SA, Yanagawa S, et al. (2006) HES1 cooperates with pRb to activate RUNX2-dependent transcription. J Bone Miner Res 21(6): 921-933. (Pubitemid 43787999)
46. Lengner CJ, Steinman HA, Gagnon J, Smith TW, Henderson JE, et al. (2006) Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling. J Cell Biol 172(6): 909-921.
47. van der Deen M, Taipaleenmaki H, Zhang Y, Teplyuk NM, Gupta A, et al. (2013) MicroRNA-34c inversely couples the biological functions of the Run-trelated transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem 288(29): 21307-21319.
48. Liu JC, Lengner CJ, Gaur T, Lou Y, Hussain S, et al. (2011) Runx2 protein expression utilizes the Runx2 P1 promoter to establish osteoprogenitor cell number for normal bone formation. J Biol Chem 286(34): 30057-30070.
49. Kang MI, Kim HS, Jung YC, Kim YH, Hong SJ, et al. (2007) Transitional CpG methylation between promoters and retroelements of tissue-specific genes during human mesenchymal cell differentiation. J Cell Biochem 102(1): 224-239.
50. Lucero CM, Vega OA, Osorio MM, Tapia JC, Antonelli M, et al. (2013) The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines. J Cell Physiol 228(4): 714-723.
51. Stein GS, Lian JB, van Wijnen AJ, Stein JL, Montecino M, et al. (2004) Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression. Oncogene 23(24): 4315-4329. (Pubitemid 38758597)
52. Thomas DM, Johnson SA, Sims NA, Trivett MK, Slavin JL, et al. (2004) Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma. J Cell Biol 167(5): 925-934. (Pubitemid 39628114)
53. Terry A, Kilbey A, Vaillant F, Stewart M, Jenkins A, et al. (2004) Conservation and expression of an alternative 3 9 exon of Runx2 encoding a novel proline-rich C-terminal domain. Gene 336(1): 115-125. (Pubitemid 38968830)
54. Mauro M, Rego MA, Boisvert RA, Esashi F, Cavallo F, et al. (2012) p21 promotes error-free replication-coupled DNA double-strand break repair. Nucleic Acids Res 40(17): 8348-8360.
55. Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387(6630): 296-299. (Pubitemid 27220766)
56. Brunelle JK, Letai A (2009) Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci 122(Pt 4): 437-441.
57. Gallaher BW, Berthold A, Klammt J, Knupfer M, Kratzsch J, et al. (2000) Expression of apoptosis and cell cycle related genes in proliferating and colcemid arrested cells of divergent lineage. Cell Mol Biol 46(1): 79-88.
58. Sato N, Mizumoto K, Maehara N, Kusumoto M, Nishio S, et al. (2000) Enhancement of drug-induced apoptosis by antisense oligodeoxynucleotides targeted against Mdm2 and p21WAF1/CIP1. Anticancer Res 20(2A): 837-842. (Pubitemid 30240642)
59. Kelly AD, Haibe-Kains B, Janeway KA, Hill KE, Howe E, et al. (2013) MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Medicine 5(2): 1-12.
60. Martin JW, Zielenska M, Stein GS, van Wijnen AJ, Squire JA (2011) The Role of RUNX2 in osteosarcoma oncogenesis. Sarcoma 2011: 282745.