DNA methylation of the homeobox genes PITX2 and SHOX2 predicts outcome in Non-small-cell lung cancer patients

Diagnostic Molecular Pathology

Volumn 21, Issue 2, 2012, Pages 93-104

  Dietrich, Dimo ^a   Hasinger, Oliver ^b   Liebenberg, Volker ^c   Field, John K ^d   Kristiansen, Glen ^a   Soltermann, Alex ^e  

^a UNIVERSITY HOSPITAL BONN   (Germany)

^b EPIGENOMICS AG   (Germany)

^c Metanomics Health GmbH   (Germany)

^d UNIVERSITY OF LIVERPOOL   (United Kingdom)

^e UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

DNA methylation; lung cancer biomarker; PITX2; prognosis; SHOX2

Indexed keywords

BIOLOGICAL MARKER; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PITX2; TRANSCRIPTION FACTOR SHOX2; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CANCER DIAGNOSIS; CANCER RISK; CANCER SURGERY; CANCER SURVIVAL; DNA METHYLATION; FEMALE; HUMAN; HUMAN TISSUE; LUNG NON SMALL CELL CANCER; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; REAL TIME POLYMERASE CHAIN REACTION;

AGED; CARCINOMA, NON-SMALL-CELL LUNG; COHORT STUDIES; DISEASE-FREE SURVIVAL; DNA METHYLATION; EPIGENESIS, GENETIC; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC ASSOCIATION STUDIES; HOMEODOMAIN PROTEINS; HUMANS; KAPLAN-MEIER ESTIMATE; LUNG NEOPLASMS; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; TISSUE ARRAY ANALYSIS; TRANSCRIPTION FACTORS; TUMOR MARKERS, BIOLOGICAL;

EID: 84861233962     PISSN: 10529551     EISSN: 15334066     Source Type: Journal    
DOI: 10.1097/PDM.0b013e318240503b     Document Type: Article

References (58)

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277-300.
2. van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009; 361:2221-2229.
3. The National Lung Screening Trial Research Team. Reduced lungcancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.
4. Harpole DH Jr, Herndon JE 2nd, Young WG Jr, et al. Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence. Cancer. 1995;76:787-796.
5. Sakurai H, Asamura H, Goya T, et al. Survival differences by gender for resected non-small cell lung cancer: a retrospective analysis of 12,509 cases in a Japanese Lung Cancer Registry study. J Thorac Oncol. 2010;5:1594-1601.
6. Asamura H, Goya T, Koshiishi Y, et al. A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers. J Thorac Oncol. 2008;3:46-52.
7. Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6:597-610. (Pubitemid 41044297)
8. Ting AH, McGarvey KM, Baylin SB. The cancer epigenome-components and functional correlates. Genes Dev. 2006;20:3215-3231.
9. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128: 683-692. (Pubitemid 46273572)
10. Baylin SB. DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol. 2005;2(Suppl 1):S4-11. (Pubitemid 43135229)
11. Maier S, Nimmrich I, Koenig T, 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. (Pubitemid 47042374)
12. Nimmrich I, Sieuwerts AM, Meijer-van Gelder ME, 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 Res Treat. 2008;111:429-437.
13. Harbeck N, Nimmrich I, Hartmann A, 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. J Clin Oncol. 2008;26:5036-5042.
14. Hartmann O, Spyratos F, Harbeck N, et al. DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy. Clin Cancer Res. 2009;15:315-323.
15. Weiss G, Cottrell S, Distler J, et al. 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. J Urol. 2009;181:1678-1685.
16. Schatz P, Dietrich D, Koenig T, et al. Development of a diagnostic microarray assay to assess the risk of recurrence of prostate cancer based on PITX2 DNA methylation. J Mol Diagn. 2010;12: 345-353.
17. Bañez LL, Sun L, van Leenders GJ, et al. Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomyprostate cancer. J Urol. 2010;184:149-156.
18. Hirose H, Ishii H, Mimori K, et al. The significance of PITX2 overexpression in human colorectal cancer. Ann Surg Oncol. 2011;18:3005-3012.
19. Quentien MH, Barlier A, Franc JL, et al. Pituitary transcription factors: from congenital deficiencies to gene therapy. J Neuroendocrinol. 2006;18:633-642. (Pubitemid 44132611)
20. Lin CR, Kioussi C, O'Connell S, et al. Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis. Nature. 1999;401:279-282.
21. Franco D, Campione M. The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases. Trends Cardiovasc Med. 2003;13:157-163. (Pubitemid 36547685)
22. Schlueter J, Brand T. Left-right axis development: examples of similar and divergent strategies to generate asymmetric morphogenesis in chick and mouse embryos. Cytogenet Genome Res. 2007;117:256-267. (Pubitemid 47202686)
23. Semina EV, Reiter R, Leysens NJ, et al. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet. 1996;14:392-399. (Pubitemid 26414582)
24. Tümer Z, Bach-Holm D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet. 2009;17:1527-1539.
25. Schmidt B, Liebenberg V, Dietrich D, et al. SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer based on bronchial aspirates. BMC Cancer. 2010;10:600.
26. Dietrich D, Kneip C, Raji O, et al. Performance evaluation of the DNA Methylation Biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirate. Int J Oncol. 2011. doi: 10.3892/ijo.2011.1264.
27. Kneip C, Schmidt B, Seegebarth A, et al. SHOX2 DNA methylation is a biomarker for the diagnosis of lung cancer in plasma. J Thorac Oncol. 2011;6:1632-1638.
28. Blaschke RJ,Monaghan AP, Schiller S, et al. SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development. Proc Natl Acad Sci U S A. 1998;95:2406-2411. (Pubitemid 28145954)
29. Blaschke RJ, Hahurij ND, Kuijper S, et al. Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation. 2007;115:1830-1838. (Pubitemid 46598896)
30. Clement-Jones M, Schiller S, Rao E, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet. 2000;9:695-702. (Pubitemid 30162753)
31. Marchini A, Rappold G, Schneider KU. SHOX at a glance: from gene to protein. Arch Physiol Biochem. 2007;113:116-123. (Pubitemid 47547384)
32. Espinoza-Lewis RA, Yu L, He F, et al. Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. Dev Biol. 2009;327:376-385.
33. Lin D, Huang Y, He F, et al. Expression survey of genes critical for tooth development in the human embryonic tooth germ. Dev Dyn. 2007;236:1307-1312. (Pubitemid 46750262)
34. Kneip C, Schmidt B, Fleischhacker M, et al. A novel method for sensitive and specific detection of DNA methylation biomarkers based on DNA restriction during PCR cycling. Biotechniques. 2009;47:737-44.
35. Schneider KU, Dietrich D, Fleischhacker M, et al. Correlation of SHOX2 gene amplification and DNA methylation in lung cancer tumors. BMC Cancer. 2011;11:102.
36. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402-408. (Pubitemid 34164012)
37. Qian J, Massion PP. Role of chromosome 3q amplification in lung cancer. J Thorac Oncol. 2008;3:212-215. (Pubitemid 351654319)
38. Levi F, Randimbison L, Te VC, et al. Second primary cancers in patients with lung carcinoma. Cancer. 1999;86:186-190. (Pubitemid 29293392)
39. Perner S, Wagner PL, Soltermann A, et al. TTF1 expression in nonsmall cell lung carcinoma: association with TTF1 gene amplification and improved survival. J Pathol. 2009;217:65-72.
40. Custodio AB, Gonza lez-Larriba JL, Bobokova J, et al. Prognostic and predictive markers of benefit from adjuvant chemotherapy in early-stage non-small cell lung cancer. J Thorac Oncol. 2009;4: 891-910.
41. Massion PP, Taflan PM, Jamshedur Rahman SM, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res. 2003;63:7113-7121. (Pubitemid 37413448)
42. Newnham GM, Conron M, McLachlan S, et al. Integrated mutation, copy number and expression profiling in resectable nonsmall cell lung cancer. BMC Cancer. 2011;11:93.
43. Bass AJ, Watanabe H, Mermel CH, et al. SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 2009;41:1238-1242.
44. Maier S, Wilbertz T, Braun M, et al. SOX2 amplification is a common event in squamous cell carcinomas of different organ sites. Hum Pathol. 2011;42:1078-1088.
45. Wilbertz T, Wagner P, Petersen K, et al. SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer. Mod Pathol. 2011;24:944-953.
46. Nanjundan M, Nakayama Y, Cheng KW, et al. Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res. 2007;67:3074-3084. (Pubitemid 46724844)
47. Sheu JJ, Lee CH, Ko JY, et al. Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2009;18:2709-2716.
48. He LR, Zhao HY, Li BK, et al. Overexpression of eIF5A-2 is an adverse prognostic marker of survival in stage I non-small-cell lung cancer patients. Int J Cancer. 2010;129:143-150.
49. Belinsky SA, Liechty KC, Gentry FD, et al. Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 2006;66:3338-3344.
50. Massion PP, Zou Y, Uner H, et al. Recurrent genomic gains in preinvasive lesions as a biomarker of risk for lung cancer. PLoS One. 2009;4:e5611.
51. McCaughan F, Pole JC, Bankier AT, et al. Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer. Am J Respir Crit Care Med. 2010;182:83-91.
52. Anagnostou VK, Syrigos KN, Bepler G, et al. Thyroid transcription factor 1 is an independent prognostic factor for patients with stage I lung adenocarcinoma. J Clin Oncol. 2009;27:271-278.
53. Martins SJ, Takagaki TY, Silva AG, et al. Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma. Lung Cancer. 2009;64:105-109.
54. Winslow MM, Dayton TL, Verhaak RG, et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature. 2011;473: 101-104.
55. Paylakhi SH, Fan JB, Mehrabian M, et al. Effect of PITX2 knockdown on transcriptome of primary human trabecular meshwork cell cultures. Mol Vis. 2011;17:1209-1221.
56. Yu Y, Fujii S, Yuan J, et al. Epigenetic regulation of ARHI in breast and ovarian cancer cells. Ann N Y Acad Sci. 2003;983: 268-277. (Pubitemid 36399339)
57. Zou CF, Jia L, Jin H, et al. Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel. BMC Cancer. 2011;11:22.
58. Wang J, Klysik E, Sood S, et al. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification.Proc Natl Acad Sci U S A. 2010;107:9753-9758.