HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

Journal of Clinical Investigation

Volumn 123, Issue 6, 2013, Pages 2488-2501

  Kostareli, Efterpi ^a,b   Holzinger, Dana ^a,c   Bogatyrova, Olga ^c   Hielscher, Thomas ^c   Wichmann, Gunnar ^d   Keck, Michaela ^e   Lahrmann, Bernd ^a,f   Grabe, Niels ^a,f   Flechtenmacher, Christa ^a   Schmidt, Christopher R ^c   Seiwert, Tanguy ^e   Dyckhoff, Gerhard ^a   Dietz, Andreas ^d   Höfler, Daniela ^c   Pawlita, Michael ^c   Benner, Axel ^c   Bosch, Franz X ^a   Plinkert, Peter ^a   Plass, Christoph ^c   Weichenhan, Dieter ^c   Hess, Jochen ^a,b   more..

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d UNIVERSITY HOSPITAL LEIPZIG   (Germany)

^e UNIVERSITY OF CHICAGO   (United States)

^f UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR GATA 4;

ADULT; AGED; ARTICLE; CANCER SURVIVAL; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; CORRELATION ANALYSIS; CPG ISLAND; DNA METHYLATION; GENETIC ASSOCIATION; GENETIC TRANSCRIPTION; GLOBAL CHANGE; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; NONHUMAN; NUCLEOTIDE SEQUENCE; OROPHARYNGEAL SQUAMOUS CELL CARCINOMA; OROPHARYNX CARCINOMA; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROMOTER REGION; QUANTITATIVE ANALYSIS; SURVIVAL PREDICTION; TISSUE MICROARRAY; VIRUS TRANSCRIPTION; WART VIRUS;

CARCINOMA, SQUAMOUS CELL; CASE-CONTROL STUDIES; CPG ISLANDS; DISEASE-FREE SURVIVAL; DNA METHYLATION; GATA4 TRANSCRIPTION FACTOR; GENE EXPRESSION REGULATION, NEOPLASTIC; HELA CELLS; HOMEODOMAIN PROTEINS; HOST-PATHOGEN INTERACTIONS; HUMAN PAPILLOMAVIRUS 16; HUMANS; KAPLAN-MEIER ESTIMATE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; OROPHARYNGEAL NEOPLASMS; PAPILLOMAVIRUS INFECTIONS; PROMOTER REGIONS, GENETIC; PROPORTIONAL HAZARDS MODELS; RECEPTORS, AMPA; RETINAL DEHYDROGENASE; SEQUENCE ANALYSIS, DNA; TRANSCRIPTION FACTORS; TRANSCRIPTOME;

EID: 84878607651     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI67010     Document Type: Article

References (91)

1. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11(1):9-22.
2. Rothenberg MS, Ellisen LW. The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest. 2012;122(6):1951-1957.
3. Masuda M, Wakasaki T, Toh S, Shimizu M, Adachi S. Chemoprevention of head and neck cancer by green tea extract: EGCG-the role of EGFR signaling and "Lipid Raft". J Oncol. 2011;2011:540148.
4. D'Souza G, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956.
5. Ernster JA, et al. Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. Laryngoscope. 2007;117(12):2115-2128.
6. Pai SI, Westra WH. Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment. Annu Rev Pathol. 2009;4:49-70.
7. Gillison ML, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407-420.
8. Ang KK, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35.
9. Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781-789.
10. Fakhry C, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261-269.
11. Vu HL, Sikora AG, Fu S, Kao J. HPV-induced oropharyngeal cancer, immune response and response to therapy. Cancer Lett. 2010;288(2):149-155.
12. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch FX. Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res. 2012;72(19):4993-5003.
13. Jung AC, et al. Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma. Int J Cancer. 2010;126(8):1882-1894.
14. Kostareli E, Holzinger D, Hess J. New concepts for translational head and neck oncology: Lessons from HPV-related oropharyngeal squamous cell carcinomas. Front Oncol. 2012;2:36.
15. Gonzalez-Ramirez I, Garcia-Cuellar C, Sanchez-Perez Y, Granados-Garcia M. DNA methylation in oral squamous cell carcinoma: molecular mechanisms and clinical implications. Oral Dis. 2011; 17(8):771-778.
16. Stephen JK, Chen KM, Havard S, Harris G, Worsham MJ. Promoter methylation in head and neck tumorigenesis. Methods Mol Biol. 2012;863:187-206.
17. Worsham MJ, et al. Delineating an epigenetic continuum in head and neck cancer [published online ahead of print March 21, 2012]. Cancer Lett. doi:10.1016/j.canlet.2012.02.018.
18. Poage GM, et al. Identification of an epigenetic profile classifier that is associated with survival in head and neck cancer. Cancer Res. 2012; 72(11):2728-2737.
19. Marsit CJ, McClean MD, Furniss CS, Kelsey KT. Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma. Int J Cancer. 2006;119(8):1761-1766.
20. Sartor MA, et al. Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis. Epigenetics. 2011;6(6):777-787.
21. Weiss D, Basel T, Sachse F, Braeuninger A, Rudack C. Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation. Mol Carcinog. 2011;50(9):680-688.
22. Gubanova E, et al. Downregulation of SMG-1 in HPV-positive head and neck squamous cell carcinoma due to promoter hypermethylation correlates with improved survival. Clin Cancer Res. 2012; 18(5):1257-1267.
23. Szklarczyk D, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 2011;39(Database issue):D561-D568.
24. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484-492.
25. Gudas LJ. Emerging roles for retinoids in regeneration and differentiation in normal and disease states. Biochim Biophys Acta. 2012;1821(1):213-221.
26. Hoffman LM, et al. BMP action in skeletogenesis involves attenuation of retinoid signaling. J Cell Biol. 2006;174(1):101-113.
27. Kim H, et al. The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer. Cancer Res. 2005;65(18):8118-8124.
28. Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA. Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med. 2012;52(4):735-746.
29. Dahlgren L, et al. Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and -negative tumors. Int J Cancer. 2003;107(2):244-249.
30. Smeets SJ, et al. Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene. 2006;25(17):2558-2564.
31. Klussmann JP, et al. Genetic signatures of HPVrelated and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res. 2009;15(5):1779-1786.
32. Wilting SM, et al. Genomic profiling identifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck. BMC Med Genomics. 2009;2:32.
33. Agrawal N, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011; 333(6046):1154-1157.
34. Stransky N, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157-1160.
35. Paz IB, Cook N, Odom-Maryon T, Xie Y, Wilczynski SP. Human papillomavirus (HPV) in head and neck cancer. An association of HPV 16 with squamous cell carcinoma of Waldeyer's tonsillar ring. Cancer. 1997;79(3):595-604.
36. Andl T, et al. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res. 1998;58(1):5-13.
37. Klussmann JP, et al. Prevalence, distribution, and viral load of human papillomavirus 16 DNA in tonsillar carcinomas. Cancer. 2001;92(11):2875-2884.
38. van Houten VM, et al. Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer. 2001;93(2):232-235.
39. Mellin H, et al. Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer. 2002;102(2):152-158.
40. Wiest T, Schwarz E, Enders C, Flechtenmacher C, Bosch FX. Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene. 2002;21(10):1510-1517.
41. Braakhuis BJ, et al. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004;96(13):998-1006.
42. Lindquist D, et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol. 2007;1(3):350-355.
43. Reimers N, et al. Combined analysis of HPVDNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer. 2007; 120(8):1731-1738.
44. Attner P, et al. The role of human papillomavirus in the increased incidence of base of tongue cancer. Int J Cancer. 2010;126(12):2879-2884.
45. Leonard SM, et al. Oncogenic human papillomavirus imposes an instructive pattern of DNA methylation changes which parallel the natural history of cervical HPV infection in young women. Carcinogenesis. 2012;33(7):1286-1293.
46. Au Yeung CL, Tsang WP, Tsang TY, Co NN, Yau PL, Kwok TT. HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53. Oncol Rep. 2010;24(6):1599-1604.
47. Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, Fuks F. Viral oncoproteins target the DNA methyltransferases. Oncogene. 2007; 26(11):1650-1655.
48. Kawai S, Amano A. Odd-skipped related 2 is epigenetically regulated in cellular quiescence. Biochem Biophys Res Commun. 2010;396(4):831-836.
49. Kawai S, Abiko Y, Amano A. Odd-skipped related 2 regulates genes related to proliferation and development. Biochem Biophys Res Commun. 2010; 398(2):184-190.
50. Agnihotri S, et al. A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas. J Exp Med. 2011;208(4):689-702.
51. Derks S, et al. Promoter methylation precedes chromosomal alterations in colorectal cancer development. Cell Oncol. 2006;28(5-6):247-257.
52. Guo M, et al. Hypermethylation of the GATA gene family in esophageal cancer. Int J Cancer. 2006; 119(9):2078-2083.
53. Wakana K, Akiyama Y, Aso T, Yuasa Y. Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis. Cancer Lett. 2006;241(2):281-288.
54. Hellebrekers DM, et al. GATA4 and GATA5 are potential tumor suppressors and biomarkers in colorectal cancer. Clin Cancer Res. 2009;15(12):3990-3997.
55. Bennett LB, et al. DNA hypermethylation accompanied by transcriptional repression in follicular lymphoma. Genes Chromosomes Cancer. 2009; 48(9):828-841.
56. Wen XZ, et al. Methylation of GATA-4 and GATA-5 and development of sporadic gastric carcinomas. World J Gastroenterol. 2010;16(10):1201-1208.
57. Psyrri A, Sasaki C, Vassilakopoulou M, Dimitriadis G, Rampias T. Future directions in research, treatment and prevention of HPV-related squamous cell carcinoma of the head and neck. Head Neck Pathol. 2012;6(suppl 1):S121-S128.
58. Taioli E, et al. Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation. BMC Cancer. 2009;9:354.
59. Dong SM, Sun DI, Benoit NE, Kuzmin I, Lerman MI, Sidransky D. Epigenetic inactivation of RASSF1A in head and neck cancer. Clin Cancer Res. 2003;9(10 pt 1):3635-3640.
60. Brumbaugh KM, et al. The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Mol Cell. 2004;14(5):585-598.
61. Gewandter JS, Bambara RA, O'Reilly MA. The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA. Cell Cycle. 2011; 10(15):2561-2567.
62. Khan SA. Cervical cancer, human papillomavirus and vaccines. Clin Oncol (R Coll Radiol). 1993; 5(6):386-390.
63. Merrick DT, Gown AM, Halbert CL, Blanton RA, McDougall JK. Human papillomavirus-immortalized keratinocytes are resistant to the effects of retinoic acid on terminal differentiation. Cell Growth Differ. 1993;4(10):831-840.
64. Creek KE, et al. Retinoic acid suppresses human papillomavirus type 16 (HPV16)-mediated transformation of human keratinocytes and inhibits the expression of the HPV16 oncogenes. Adv Exp Med Biol. 1994;354:19-35.
65. Creek KE, Geslani G, Batova A, Pirisi L. Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes. Adv Exp Med Biol. 1995;375:117-135.
66. Choo CK, Rorke EA, Eckert RL. Retinoid regulation of cell differentiation in a series of human papillomavirus type 16-immortalized human cervical epithelial cell lines. Carcinogenesis. 1995;16(2):375-381.
67. Narayanan BA, Holladay EB, Nixon DW, Mauro CT. The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells. Life Sci. 1998;63(7):565-573.
68. Touma SE, Perner S, Rubin MA, Nanus DM, Gudas LJ. Retinoid metabolism and ALDH1A2 (RALDH2) expression are altered in the transgenic adenocarcinoma mouse prostate model. Biochem Pharmacol. 2009;78(9):1127-1138.
69. Liang D, Jia W, Li J, Li K, Zhao Q. Retinoic acid signaling plays a restrictive role in zebrafish primitive myelopoiesis. PLoS One. 2012;7(2):e30865.
70. Neto A, Mercader N, Gomez-Skarmeta JL. The Osr1 and Osr2 genes act in the pronephric anlage downstream of retinoic acid signaling and upstream of Wnt2b to maintain pectoral fin development. Development. 2012;139(2):301-311.
71. Mauney JR, Ramachandran A, Yu RN, Daley GQ, Adam RM, Estrada CR. All-trans retinoic acid directs urothelial specification of murine embryonic stem cells via GATA4/6 signaling mechanisms. PLoS One. 2010;5(7):e11513.
72. Ghatpande S, Brand T, Zile M, Evans T. Bmp2 and Gata4 function additively to rescue heart tube development in the absence of retinoids. Dev Dyn. 2006;235(8):2030-2039.
73. Wang GF, Nikovits W Jr, Bao ZZ, Stockdale FE. Irx4 forms an inhibitory complex with the vitamin D and retinoic X receptors to regulate cardiac chamber-specific slow MyHC3 expression. J Biol Chem. 2001;276(31):28835-28841.
74. Cheng Z, et al. Two novel mutations of the IRX4 gene in patients with congenital heart disease. Hum Genet. 2011;130(5):657-662.
75. Wirth LJ, Haddad RI, Posner MR. Progress and perspectives in chemoprevention of head and neck cancer. Expert Rev Anticancer Ther. 2003;3(3):339-355.
76. Armstrong WB, Meyskens FL. Chemoprevention of head and neck cancer. Otolaryngol Head Neck Surg. 2000;122(5):728-735.
77. Guo Y, et al. A retinoic acid-rich tumor microenvironment provides clonal survival cues for tumor-specific CD8+ T cells. Cancer Res. 2012; 72(20):5230-5239.
78. Wansom D, et al. Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer. Arch Otolaryngol Head Neck Surg. 2010; 136(12):1267-1273.
79. Wansom D, et al. Infiltrating lymphocytes and human papillomavirus-16- associated oropharyngeal cancer. Laryngoscope. 2012;122(1):121-127.
80. Napoli JL. Physiological insights into all-trans-retinoic acid biosynthesis. Biochim Biophys Acta. 2012; 1821(1):152-167.
81. Williams SJ, Cvetkovic D, Hamilton TC. Vitamin A metabolism is impaired in human ovarian cancer. Gynecol Oncol. 2009;112(3):637-645.
82. Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993; 15(3):532-534, 536-537.
83. Sotlar K, et al. Detection and typing of human papillomavirus by e6 nested multiplex PCR. J Clin Microbiol. 2004;42(7):3176-3184.
84. Gebhard C, et al. Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia. Cancer Res. 2006;66(12):6118-6128.
85. Schilling E, Rehli M. Global, comparative analysis of tissue-specific promoter CpG methylation. Genomics. 2007;90(3):314-323.
86. Ritchie ME, et al. A comparison of background correction methods for two-colour microarrays. Bioinformatics. 2007;23(20):2700-2707.
87. Kuhmann C, Weichenhan D, Rehli M, Plass C, Schmezer P, Popanda O. DNA methylation changes in cells regrowing after fractioned ionizing radiation. Radiother Oncol. 2011;101(1):116-121.
88. Tusher VG, Tibshirani R, Chu G. Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001; 98(9):5116-5121.
89. Robinson JT, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29(1):24-26.
90. Ehrich M, et al. Quantitative high-throughput analysis of DNA methylation patterns by basespecific cleavage and mass spectrometry. Proc Natl Acad Sci U S A. 2005;102(44):15785-15790.
91. Roesch Ely M, et al. Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol. 2005;84(2-3):431-444.