PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma

Oncotarget

Volumn 7, Issue 46, 2016, Pages 75827-75838

  Sailer, Verena ^a   Holmes, Emily Eva ^b   Gevensleben, Heidrun ^b   Goltz, Diane ^b   Dröge, Freya ^c   De Vos, Luka ^b   Franzen, Alina ^b   Schröck, Friederike ^d   Bootz, Friedrich ^b   Kristiansen, Glen ^b   Schröck, Andreas ^b   Dietrich, Dimo ^b  

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b UNIVERSITY HOSPITAL BONN   (Germany)

^c UNIVERSITY HOSPITAL ESSEN   (Germany)

^d LVR Clinic Bonn   (Germany)

Author keywords

Biomarker; DNA methylation; Head and neck squamous cell carcinoma; PANCR; PITX2

Indexed keywords

BISULFITE; DNA; LONG UNTRANSLATED RNA; PROTEIN P16; TRANSCRIPTION FACTOR PITX2; HOMEODOMAIN PROTEIN; TRANSCRIPTION FACTOR; TUMOR MARKER;

ADULT; AGE; ARTICLE; CANCER GRADING; CANCER MORTALITY; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; CONTROLLED STUDY; DISTANT METASTASIS; DNA METHYLATION; FEMALE; GENE; GENE EXPRESSION; GENE LOCATION; GENETIC ASSOCIATION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MORTALITY RISK; OVERALL SURVIVAL; PANCR GENE; PITX2 GENE; REAL TIME POLYMERASE CHAIN REACTION; SMOKING; TUMOR INVASION; TUMOR LOCALIZATION; TUMOR SUPPRESSOR GENE; AGED; CANCER STAGING; GENETIC ASSOCIATION STUDY; GENETICS; HEAD AND NECK TUMOR; KAPLAN MEIER METHOD; MORTALITY; PATHOLOGY; PROGNOSIS; PROPORTIONAL HAZARDS MODEL; REPRODUCIBILITY; RISK FACTOR; SQUAMOUS CELL CARCINOMA;

ADULT; AGED; BIOMARKERS, TUMOR; CARCINOMA, SQUAMOUS CELL; DNA METHYLATION; FEMALE; GENETIC ASSOCIATION STUDIES; HEAD AND NECK NEOPLASMS; HOMEODOMAIN PROTEINS; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; NEOPLASM GRADING; NEOPLASM STAGING; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; REPRODUCIBILITY OF RESULTS; RISK FACTORS; RNA, LONG NONCODING; TRANSCRIPTION FACTORS;

EID: 84996928563     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.12417     Document Type: Article

References (61)

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66:7-30.
2. IARC. (2005). Pathology and Genetics of Head and Neck Tumours.
3. Mashberg A, Boffetta P, Winkelman R, Garfinkel L. Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans. Cancer. 1993; 72:1369-1375.
4. Vokes EE, Agrawal N, Seiwert TY. HPV-Associated Head and Neck Cancer. Journal of the National Cancer Institute. 2015; 107:djv344.
5. zur Hausen H. Human papillomaviruses and their possible role in squamous cell carcinomas. Current topics in microbiology and immunology. 1977; 78:1-30.
6. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. Journal of the National Cancer Institute. 2000; 92:709-720.
7. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015; 517:576-582.
8. Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008; 371:1695-1709.
9. Whang SN, Filippova M, Duerksen-Hughes P. Recent Progress in Therapeutic Treatments and Screening Strategies for the Prevention and Treatment of HPVAssociated Head and Neck Cancer. Viruses. 2015; 7:5040-5065.
10. Olthof NC, Straetmans JM, Snoeck R, Ramaekers FC, Kremer B, Speel EJ. Next-generation treatment strategies for human papillomavirus-related head and neck squamous cell carcinoma: where do we go? Rev Med Virol. 2012; 22:88-105.
11. De Felice F, Thomas C, Barrington S, Pathmanathan A, Lei M, Urbano TG. Analysis of loco-regional failures in head and neck cancer after radical radiation therapy. Oral oncology. 2015; 51:1051-1055.
12. Sacco AG, Cohen EE. Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Journal of clinical oncology. 2015; 33:3305-3313.
13. Gentzler R, Hall R, Kunk PR, Gaughan E, Dillon P, SlingluffCL, Jr., Rahma OE. Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in solid tumors. Immunotherapy. 2016; 8:583-600.
14. Tanguy Y, Seiwert RIH, Gupta S, Mehra R, Tahara M, Berger R, Lee S-H, Burtness B, Le DT, Heath K, Blum A, Dolled-Filhart M, Emancipator K, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. J Clin Oncol 33, 2015. 2015.
15. Lohaus F, Linge A, Tinhofer I, Budach V, Gkika E, Stuschke M, Balermpas P, Rodel C, Avlar M, Grosu AL, Abdollahi A, Debus J, Bayer C, Belka C, Pigorsch S, Combs SE, et al. HPV16 DNA status is a strong prognosticator of locoregional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Radiotherapy and oncology. 2014; 113:317-323.
16. Balermpas P, Rodel F, Rodel C, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Gkika E, Stuschke M, Avlar M, Grosu AL, Abdollahi A, Debus J, Bayer C, et al. CD8+ tumour-infiltrating lymphocytes in relation to HPV status and clinical outcome in patients with head and neck cancer after postoperative chemoradiotherapy: A multicentre study of the German cancer consortium radiation oncology group (DKTK-ROG). International journal of cancer. 2016; 138:171-181.
17. Reddy RB, Bhat AR, James BL, Govindan SV, Mathew R, Dr R, Hedne N, Illiayaraja J, Kekatpure V, Khora SS, Hicks W, Tata P, Kuriakose MA, Suresh A. Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer. PloS one. 2016; 11:e0147409.
18. Chau NG, Li YY, Jo VY, Rabinowits G, Lorch JH, Tishler RB, Margalit DN, Schoenfeld JD, Annino DJ, Goguen L, Thomas T, Becker H, Haddad T, Krane JF, Lindeman NI, Shapiro GI, et al. Incorporation of next-generation sequencing into routine clinical care to direct treatment of head and neck squamous cell carcinoma. Clinical cancer research. 2016.
19. Rauch TA, Zhong X, Wu X, Wang M, Kernstine KH, Wang Z, Riggs AD, Pfeifer GP. High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105:252-257.
20. Ting AH, McGarvey KM, Baylin SB. The cancer epigenome-components and functional correlates. Genes & development. 2006; 20:3215-3231.
21. Bienkowski M, BerghoffAS, Marosi C, Wohrer A, Heinzl H, Hainfellner JA, Preusser M. Clinical Neuropathology practice guide 5-2015: MGMT methylation pyrosequencing in glioblastoma: unresolved issues and open questions. Clinical neuropathology. 2015; 34:250-257.
22. Brigliadori G, Foca F, Dall'Agata M, Rengucci C, Melegari E, Cerasoli S, Amadori D, Calistri D, Faedi M. Defining the cutoffvalue of MGMT gene promoter methylation and its predictive capacity in glioblastoma. Journal of neurooncology. 2016.
23. Quentien MH, Barlier A, Franc JL, Pellegrini I, Brue T, Enjalbert A. Pituitary transcription factors: from congenital deficiencies to gene therapy. Journal of neuroendocrinology. 2006; 18:633-642.
24. Lin CR, Kioussi C, O'Connell S, Briata P, Szeto D, Liu F, Izpisua-Belmonte JC, Rosenfeld MG. Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature. 1999; 401:279-282.
25. Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, Ohgi KA, Lin C, Gleiberman A, Wang J, Brault V, Ruiz-Lozano P, Nguyen HD, Kemler R, Glass CK, Wynshaw-Boris A, et al. Identification of a Wnt/Dvl/beta-Catenin→ Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. 2002; 111:673-685.
26. Liu Y, Huang Y, Zhu GZ. Cyclin A1 is a transcriptional target of PITX2 and overexpressed in papillary thyroid carcinoma. Molecular and cellular biochemistry. 2013; 384:221-227.
27. Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP. Methylation profiling in acute myeloid leukemia. Blood. 2001; 97:2823-2829.
28. Nimmrich I, Sieuwerts AM, Meijer-van Gelder ME, Schwope I, Bolt-de Vries J, Harbeck N, Koenig T, Hartmann O, Kluth A, Dietrich D, Magdolen V, Portengen H, Look MP, Klijn JG, Lesche R, Schmitt M, et al. DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients. Breast cancer research and treatment. 2008; 111:429-437.
29. Maier S, Nimmrich I, Koenig T, Eppenberger-Castori S, Bohlmann I, Paradiso A, Spyratos F, Thomssen C, Mueller V, Nahrig J, Schittulli F, Kates R, Lesche R, Schwope I, Kluth A, Marx A, et al. DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifen-treated, node-negative breast cancer patients-Technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group. Eur J Cancer. 2007; 43:1679-1686.
30. Harbeck N, Nimmrich I, Hartmann A, Ross JS, Cufer T, Grutzmann R, Kristiansen G, Paradiso A, Hartmann O, Margossian A, Martens J, Schwope I, Lukas A, Muller V, Milde-Langosch K, Nahrig J, et al. Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients. Journal of clinical oncology. 2008; 26:5036-5042.
31. Hartmann O, Spyratos F, Harbeck N, Dietrich D, Fassbender A, Schmitt M, Eppenberger-Castori S, Vuaroqueaux V, Lerebours F, Welzel K, Maier S, Plum A, Niemann S, Foekens JA, Lesche R, Martens JW. DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracyclinebased chemotherapy. Clinical cancer research. 2009; 15:315-323.
32. Weiss G, Cottrell S, Distler J, Schatz P, Kristiansen G, Ittmann M, Haefliger C, Lesche R, Hartmann A, Corman J, Wheeler T. DNA methylation of the PITX2 gene promoter region is a strong independent prognostic marker of biochemical recurrence in patients with prostate cancer after radical prostatectomy. The Journal of urology. 2009; 181:1678-1685.
33. Banez LL, Sun L, van Leenders GJ, Wheeler TM, Bangma CH, Freedland SJ, Ittmann MM, Lark AL, Madden JF, Hartman A, Weiss G, Castanos-Velez E. Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer. The Journal of urology. 2010; 184:149-156.
34. Fung FK, Chan DW, Liu VW, Leung TH, Cheung AN, Ngan HY. Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PloS one. 2012; 7:e37076.
35. Weller M, Tabatabai G, Kastner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bahr O, Platten M, Tonn JC, Schlegel U, et al. MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial. Clinical cancer research. 2015; 21:2057-2064.
36. Costa FF. Non-coding RNAs: Meet thy masters. BioEssays: news and reviews in molecular, cellular and developmental biology. 2010; 32:599-608.
37. Maia BM, Rocha RM, Calin GA. Clinical significance of the interaction between non-coding RNAs and the epigenetics machinery: challenges and opportunities in oncology. Epigenetics. 2014; 9:75-80.
38. Ragusa M, Barbagallo C, Statello L, Condorelli AG, Battaglia R, Tamburello L, Barbagallo D, Di Pietro C, Purrello M. Non-coding landscapes of colorectal cancer. World journal of gastroenterology. 2015; 21:11709-11739.
39. Amaral PP, Dinger ME, Mercer TR, Mattick JS. The eukaryotic genome as an RNA machine. Science. 2008; 319:1787-1789.
40. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS. Non-coding RNAs: regulators of disease. The Journal of pathology. 2010; 220:126-139.
41. St Laurent G, Wahlestedt C, Kapranov P. The Landscape of long noncoding RNA classification. Trends in genetics: TIG. 2015; 31:239-251.
42. Gore-Panter SR, Hsu J, Barnard J, Moravec CS, Van Wagoner DR, Chung MK, Smith JD. PANCR, the PITX2 Adjacent Noncoding RNA, Is Expressed in Human Left Atria and Regulates PITX2c Expression. Circulation Arrhythmia and electrophysiology. 2016; 9.
43. Dietrich D, Hasinger O, Liebenberg V, Field JK, Kristiansen G, Soltermann A. DNA methylation of the homeobox genes PITX2 and SHOX2 predicts outcome in non-small-cell lung cancer patients. Diagn Mol Pathol. 2012; 21:93-104.
44. Dietrich D, Hasinger O, Banez LL, Sun L, van Leenders GJ, Wheeler TM, Bangma CH, Wernert N, Perner S, Freedland SJ, Corman JM, Ittmann MM, Lark AL, Madden JF, Hartmann A, Schatz P, et al. Development and clinical validation of a real-time PCR assay for PITX2 DNA methylation to predict prostate-specific antigen recurrence in prostate cancer patients following radical prostatectomy. The Journal of molecular diagnostics: JMD. 2013; 15:270-279.
45. Curado MP, Hashibe M. Recent changes in the epidemiology of head and neck cancer. Current opinion in oncology. 2009; 21:194-200.
46. Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, Denkert C. CutoffFinder: a comprehensive and straightforward Web application enabling rapid biomarker cutoffoptimization. PloS one. 2012; 7:e51862.
47. Salazar CR, Anayannis N, Smith RV, Wang Y, Haigentz M, Jr., Garg M, SchiffBA, Kawachi N, Elman J, Belbin TJ, Prystowsky MB, Burk RD, Schlecht NF. Combined P16 and human papillomavirus testing predicts head and neck cancer survival. Int J Cancer. 2014; 135:2404-2412.
48. Sun W, Califano JA. Sequencing the head and neck cancer genome: implications for therapy. Annals of the New York Academy of Sciences. 2014; 1333:33-42.
49. Expert Panel on Radiation O-H, Neck, Salama JK, Saba N, Quon H, Garg MK, Lawson J, McDonald MW, Ridge JA, Smith RV, Yeung AR, Yom SS, Beitler JJ. ACR appropriateness criteria(R) adjuvant therapy for resected squamous cell carcinoma of the head and neck. Oral oncology. 2011; 47:554-559.
50. Busch CJ, Laban S, Knecht R, Hoffmann TK. [Immunotherapeutic studies of head and neck tumors: Highlights of the 2016 ASCO Annual Meeting]. HNO. 2016.
51. Schayek H, Bentov I, Jacob-Hirsch J, Yeung C, Khanna C, Helman LJ, Plymate SR, Werner H. Global methylation analysis identifies PITX2 as an upstream regulator of the androgen receptor and IGF-I receptor genes in prostate cancer. Hormone and metabolic research. 2012; 44:511-519.
52. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489:519-525.
53. Hirose H, Ishii H, Mimori K, Tanaka F, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. The significance of PITX2 overexpression in human colorectal cancer. Ann Surg Oncol. 2011; 18:3005-3012.
54. Zhang JX, Tong ZT, Yang L, Wang F, Chai HP, Zhang F, Xie MR, Zhang AL, Wu LM, Hong H, Yin L, Wang H, Wang HY, Zhao Y. PITX2: a promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma. International journal of cancer. 2013; 132:2567-2577.
55. Zhang JX, Chen ZH, Xu Y, Chen JW, Weng HW, Yun M, Zheng ZS, Chen C, Wu BL, Li EM, Fu JH, Ye S, Xie D. Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem-celllike Phenotype via Dysregulation of PITX2. Clinical cancer research. 2016.
56. Yan K, Arfat Y, Li D, Zhao F, Chen Z, Yin C, Sun Y, Hu L, Yang T, Qian A. Structure Prediction: New Insights into Decrypting Long Noncoding RNAs. International journal of molecular sciences. 2016; 17.
57. Kulis M, Queiros AC, Beekman R, Martin-Subero JI. Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. Biochimica et biophysica acta. 2013; 1829:1161-1174.
58. Angadi PV, Savitha JK, Rao SS, Sivaranjini Y. Oral field cancerization: current evidence and future perspectives. Oral and maxillofacial surgery. 2012; 16:171-180.
59. van Oijen MG, Rijksen G, ten Broek FW, Slootweg PJ. Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse. Oral diseases. 1998; 4:4-8.
60. Merlano MC, Denaro N, Vivenza D, Monteverde M, Russi E, Lerda W, Comino A, Lo Nigro C. p16 cutoffin head and neck squamous cell carcinoma: correlation between tumor and patient characteristics and outcome. The International journal of biological markers. 2015:0.
61. Holmes EE, Jung M, Meller S, Leisse A, Sailer V, Zech J, Mengdehl M, Garbe LA, Uhl B, Kristiansen G, Dietrich D. Performance evaluation of kits for bisulfite-conversion of DNA from tissues, cell lines, FFPE tissues, aspirates, lavages, effusions, plasma, serum, and urine. PloS one. 2014; 9:e93933.