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01-12-2016 | REPORT

WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report

Authors: Ilda Patrícia Ribeiro, Francisco Caramelo, Francisco Marques, Ana Domingues, Margarida Mesquita, Leonor Barroso, Hugo Prazeres, Maria José Julião, Isabel Poiares Baptista, Artur Ferreira, Joana Barbosa Melo, Isabel Marques Carreira

Published in: Cellular Oncology | Issue 6/2016

Abstract

Purpose

Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive malignancy with a heterogeneous clinical behavior. Based on the paucity of specific early diagnostic and prognostic biomarkers, which hampers the appropriate treatment and, ultimately the development of novel targeted therapies, we aimed at identifying such biomarkers through a genetic and epigenetic analysis of these tumors.

Methods

93 primary OSCCs were subjected to DNA copy number alteration (CNA) and methylation status analyses using methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA). The genetic and epigenetic OSCC profiles obtained were associated with the patients’ clinic-pathological features.

Results

We found that WT1 gene promoter methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene promoter methylation serve as predictors of a worse prognosis. GATA5 gene promoter methylation was found to be significantly associated with a shorter survival rate. In addition, we found that PAX5 gene promoter methylation was significantly associated with tongue tumors. To the best of our knowledge, this is the first study that highlights this specific set of genes as epigenetic diagnostic and prognostic biomarkers in OSCC.

Conclusions

Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.

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L. M. Arantes, A. C. de Carvalho, M. E. Melendez, C. C. Centrone, J. F. Gois-Filho, T. N. Toporcov, D. N. Caly, E. H. Tajara, E. M. Goloni-Bertollo, A. L. Carvalho, And Gencapo, validation of methylation markers for diagnosis of oral cavity cancer. Eur. J. Cancer 51, 632–641 (2015). doi:10.1016/j.ejca.2015.01.060 CrossRefPubMed

A.K. Markopoulos, Current aspects on oral squamous cell carcinoma. Open Dent. J. 6, 126–130 (2012) doi:10.2174/1874210601206010126

C. Salazar, R. Nagadia, P. Pandit, J. Cooper-White, N. Banerjee, N. Dimitrova, W. B. Coman, C. Punyadeera, A novel saliva-based microRNA biomarker panel to detect head and neck cancers. Cell. Oncol. 37, 331–338 (2014). doi:10.1007/s13402-014-0188-2 CrossRef

K. Mohankumar, S. Pajaniradje, S. Sridharan, V. K. Singh, L. Ronsard, A. C. Banerjea, B. C. Selvanesan, M. S. Coumar, L. Periyasamy, R. Rajagopalan, Apoptosis induction by an analog of curcumin (BDMC-A) in human laryngeal carcinoma cells through intrinsic and extrinsic pathways. Cell. Oncol. 37, 439–454 (2014). doi:10.1007/s13402-014-0207-3 CrossRef

D. Pulte, H. Brenner, Changes in survival in head and neck cancers in the late 20th and early twenty-first century: a period analysis. Oncologist 15, 994–1001 (2010). doi:10.1634/theoncologist.2009-0289 CrossRefPubMedPubMedCentral

T. Nakaoka, A. Ota, T. Ono, S. Karnan, H. Konishi, A. Furuhashi, Y. Ohmura, Y. Yamada, Y. Hosokawa, Y. Kazaoka, Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells. Cell. Oncol. 37, 119–129 (2014). doi:10.1007/s13402-014-0167-7 CrossRef

Y. Tokumaru, K. Yamashita, M. Osada, S. Nomoto, D. I. Sun, Y. Xiao, M. O. Hoque, W. H. Westra, J. A. Califano, D. Sidransky, Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res. 64, 5982–5987 (2004). doi:10.1158/0008-5472.CAN-04-0993 CrossRefPubMed

C. R. Leemans, B. J. Braakhuis, R. H. Brakenhoff, The molecular biology of head and neck cancer. Nat. Rev. Cancer 11, 9–22 (2011). doi:10.1038/nrc2982 CrossRefPubMed

T. Bezabeh, O. Odlum, R. Nason, P. Kerr, D. Sutherland, R. Patel, I. C. Smith, Prediction of treatment response in head and neck cancer by magnetic resonance spectroscopy. AJNR Am. J. Neuroradiol. 26, 2108–2113 (2005)PubMed

10.

R. J. Nobre, E. Cruz, O. Real, L. P. de Almeida, T. C. Martins, Characterization of common and rare human papillomaviruses in Portuguese women by the polymerase chain reaction, restriction fragment length polymorphism and sequencing. J. Med. Virol. 82, 1024–1032 (2010). doi:10.1002/jmv.21756 CrossRefPubMed

11.

A. O. Nygren, N. Ameziane, H. M. Duarte, R. N. Vijzelaar, Q. Waisfisz, C. J. Hess, J. P. Schouten, A. Errami, Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences. Nucleic Acids Res. 33, e128 (2005). doi:10.1093/nar/gni127 CrossRefPubMedPubMedCentral

12.

I. P. Ribeiro, F. Marques, F. Caramelo, J. Ferrao, H. Prazeres, M. J. Juliao, W. Rifi, S. Savola, J. B. de Melo, I. P. Baptista, I. M. Carreira, Genetic imbalances detected by multiplex ligation-dependent probe amplification in a cohort of patients with oral squamous cell carcinoma-the first step towards clinical personalized medicine. Tumour Biol. 35, 4687–4695 (2014). doi:10.1007/s13277-014-1614-9 PubMed

13.

I. P. Ribeiro, F. Marques, F. Caramelo, J. Pereira, M. Patricio, H. Prazeres, J. Ferrao, M. J. Juliao, M. Castelo-Branco, J. B. de Melo, I. P. Baptista, I. M. Carreira, Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management. Cell. Oncol. 37, 29–39 (2014). doi:10.1007/s13402-013-0161-5 CrossRef

14.

M. Chmelarova, E. Dvorakova, J. Spacek, J. Laco, M. Mzik, V. Palicka, Promoter methylation of GATA4, WIF1, NTRK1 and other selected tumour suppressor genes in ovarian cancer. Folia Biol. 59, 87–92 (2013)

15.

S. Maruya, J. P. Issa, R. S. Weber, D. I. Rosenthal, J. C. Haviland, R. Lotan, A. K. El-Naggar, Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin. Cancer Res. 10, 3825–3830 (2004). doi:10.1158/1078-0432.CCR-03-0370 CrossRefPubMed

16.

S. Sharma, T. K. Kelly, P. A. Jones, Epigenetics in cancer. Carcinogenesis 31, 27–36 (2010). doi:10.1093/carcin/bgp220 CrossRefPubMed

17.

A. S. Ho, S. Turcan, T. A. Chan, Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management. Onco Targets Ther. 6, 223–232 (2013). doi:10.2147/OTT.S34680 PubMedPubMedCentral

18.

M. J. Worsham, J. K. Stephen, K. M. Chen, S. Havard, V. Shah, G. Gardner, V. G. Schweitzer, Delineating an epigenetic continuum in head and neck cancer. Cancer Lett. 342, 178–184 (2014). doi:10.1016/j.canlet.2012.02.018 CrossRefPubMed

19.

M. Federico and L. Bagella, Histone deacetylase inhibitors in the treatment of hematological malignancies and solid tumors. J. Biomed. Biotechnol. 2011, 475641 (2011) doi:10.1155/2011/475641

20.

Y. Oji, H. Yamamoto, M. Nomura, Y. Nakano, A. Ikeba, S. Nakatsuka, S. Abeno, E. Kiyotoh, T. Jomgeow, M. Sekimoto, R. Nezu, Y. Yoshikawa, Y. Inoue, N. Hosen, M. Kawakami, A. Tsuboi, Y. Oka, H. Ogawa, S. Souda, K. Aozasa, M. Monden, H. Sugiyama, Overexpression of the Wilms’ tumor gene WT1 in colorectal adenocarcinoma. Cancer Sci. 94, 712–717 (2003)CrossRefPubMed

21.

H. Sugiyama, WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn. J. Clin. Oncol. 40, 377–387 (2010) doi:10.1093/jjco/hyp194

22.

L. Yang, Y. Han, F. Suarez Saiz, M. D. Minden, A tumor suppressor and oncogene: the WT1 story. Leukemia 21, 868–876 (2007). doi:10.1038/sj.leu.2404624 PubMed

23.

X. W. Qi, F. Zhang, H. Wu, J. L. Liu, B. G. Zong, C. Xu, J. Jiang, Wilms’ tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis. Sci. Rep. 5, 8924 (2015). doi:10.1038/srep08924 CrossRefPubMedPubMedCentral

24.

S. Yip, J. Miao, D. P. Cahill, A. J. Iafrate, K. Aldape, C. L. Nutt, D. N. Louis, MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin. Cancer Res. 15, 4622–4629 (2009). doi:10.1158/1078-0432.CCR-08-3012 CrossRefPubMedPubMedCentral

25.

I. Peters, N. Dubrowinskaja, M. Kogosov, M. Abbas, J. Hennenlotter, C. von Klot, A. S. Merseburger, A. Stenzl, R. Scherer, M. A. Kuczyk, J. Serth, Decreased GATA5 mRNA expression associates with CpG island methylation and shortened recurrence-free survival in clear cell renal cell carcinoma. BMC Cancer 14, 101 (2014). doi:10.1186/1471-2407-14-101 CrossRefPubMedPubMedCentral

26.

I. Peters, K. Gebauer, N. Dubrowinskaja, F. Atschekzei, M. W. Kramer, J. Hennenlotter, H. Tezval, M. Abbas, R. Scherer, A. S. Merseburger, A. Stenzl, M. A. Kuczyk, J. Serth, GATA5 CpG island hypermethylation is an independent predictor for poor clinical outcome in renal cell carcinoma. Oncol. Rep. 31, 1523–1530 (2014). doi:10.3892/or.2014.3030 PubMedPubMedCentral

27.

R. Zheng, G. A. Blobel, G. A. T. A. Transcription Factors, And cancer. Genes Cancer 1, 1178–1188 (2010). doi:10.1177/1947601911404223 CrossRefPubMedPubMedCentral

28.

R. Guerrero-Preston, C. Michailidi, L. Marchionni, C. R. Pickering, M. J. Frederick, J. N. Myers, S. Yegnasubramanian, T. Hadar, M. G. Noordhuis, V. Zizkova, E. Fertig, N. Agrawal, W. Westra, W. Koch, J. Califano, V. E. Velculescu, D. Sidransky, Key tumor suppressor genes inactivated by "greater promoter" methylation and somatic mutations in head and neck cancer. Epigenetics 9, 1031–1046 (2014). doi:10.4161/epi.29025 CrossRefPubMedPubMedCentral

29.

M. J. Worsham, H. Ali, J. Dragovic, V. P. Schweitzer, Molecular characterization of head and neck cancer: how close to personalized targeted therapy? Mol. Diagn. Ther. 16, 209–222 (2012). doi:10.2165/11635330-000000000-00000 CrossRefPubMedPubMedCentral

30.

S. I. Pai, W. H. Westra, Molecular pathology of head and neck cancer: implications for diagnosis, prognosis, and treatment. Annu. Rev. Pathol. 4, 49–70 (2009)CrossRefPubMedPubMedCentral

31.

K. T. Robbins, G. Clayman, P. A. Levine, J. Medina, R. Sessions, A. Shaha, P. Som, G. T. Wolf, H. American, S. Neck, O.-H. American Academy, Of and S. Neck, neck dissection classification update: revisions proposed by the American head and neck society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch. Otolaryngol. Head Neck Surg. 128, 751–758 (2002)CrossRef

32.

Cancer Genome Atlas Network, comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517, 576–582 (2015) doi:10.1038/nature14129

33.

S. B. Chinn, J. N. Myers, Oral cavity carcinoma: current management, controversies, and future directions. J. Clin. Oncol. 33, 3269–3276 (2015). doi:10.1200/JCO.2015.61.2929 CrossRefPubMed

Title: WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report
Authors: Ilda Patrícia Ribeiro
Francisco Caramelo
Francisco Marques
Ana Domingues
Margarida Mesquita
Leonor Barroso
Hugo Prazeres
Maria José Julião
Isabel Poiares Baptista
Artur Ferreira
Joana Barbosa Melo
Isabel Marques Carreira
Publication date: 01-12-2016
Publisher: Springer Netherlands
Published in: Cellular Oncology / Issue 6/2016
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-016-0293-5

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