Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients

Efterpi Kostareli, Thomas Hielscher, Manuela Zucknick, Lorena Baboci, Gunnar Wichmann, Dana Holzinger, Oliver Mücke, Michael Pawlita, Annarosa Del Mistro, Paolo Boscolo-Rizzo, Maria Cristina Da Mosto, Giancarlo Tirelli, Peter Plinkert, Andreas Dietz, Christoph Plass, Dieter Weichenhan, Jochen Hess

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17 Citations (Scopus)

Abstract

Infection with high-risk types of human papilloma virus (HPV) is currently the best-established prognostic marker for head and neck squamous cell carcinoma (HNSCC), one of the most common and lethal human malignancies worldwide. Clinical trials have been launched to address the concept of treatment de-escalation for HPV-positive HNSCC with the final aim to reduce treatment related toxicity and debilitating long-term impacts on the quality of life. However, HPV-related tumors are mainly restricted to oropharyngeal SCC (OPSCC) and there is an urgent need to establish reliable biomarkers for all patients at high risk for treatment failure. A patient cohort (n = 295) with mainly non-OPSCC (72.9%) and a low prevalence of HPV16-related tumors (8.8%) was analyzed by MassARRAY to determine a previously established prognostic methylation score (MS). Kaplan-Meier revealed a highly significant correlation between a high MS and a favorable survival for OPSCC (P = 0.0004) and for non-OPSCC (P<0.0001), which was confirmed for all HNSCC by multivariate Cox regression models (HR: 9.67, 95% CI [4.61-20.30], P<0.0001). Next, we established a minimal methylation signature score (MMSS), which consists of ten most informative of the originally 62 CpG units used for the MS. The prognostic value of the MMSS was confirmed by Kaplan-Meier analysis for all HNSCC (P<0.0001) and non-OPSCC (P = 0.0002), and was supported by multivariate Cox regression models for all HNSCC (HR: 2.15, 95% CI [1.36-3.41], P = 0.001). In summary, the MS and the MMSS exhibit an excellent performance as prognosticators for survival, which is not limited by the anatomical site, and both could be implemented in future clinical trials.

Original languageEnglish
Pages (from-to)61-73
JournalEpigenetics
Volume11
Issue number1
Early online date19 Jan 2016
DOIs
Publication statusEarly online date - 19 Jan 2016
Externally publishedYes

Keywords

  • Biomarkers, Tumor/genetics
  • Carcinoma, Squamous Cell/genetics
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Female
  • Head and Neck Neoplasms/genetics
  • Human papillomavirus 16
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic
  • Proportional Hazards Models

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  • Cite this

    Kostareli, E., Hielscher, T., Zucknick, M., Baboci, L., Wichmann, G., Holzinger, D., Mücke, O., Pawlita, M., Del Mistro, A., Boscolo-Rizzo, P., Da Mosto, M. C., Tirelli, G., Plinkert, P., Dietz, A., Plass, C., Weichenhan, D., & Hess, J. (2016). Gene promoter methylation signature predicts survival of head and neck squamous cell carcinoma patients. Epigenetics, 11(1), 61-73. https://doi.org/10.1080/15592294.2015.1137414