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Prognostische und prädiktive Methylierungsbiomarker für HNSCC

Epigenomische Diagnostika für Plattenepithelkarzinome des Kopf- und Halsbereichs (HNSCC)

Prognostic and predictive methylation biomarkers in HNSCC

Epigenomic diagnostics for head and neck squamous cell carcinoma (HNSCC)

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Zusammenfassung

Hintergrund

Prognostische und prädiktive Biomarker sind für eine personalisierte Therapiesteuerung beim Plattenepithelkarzinom des Kopf- und Halsbereichs (HNSCC) von klinischem Interesse.

Fragestellung

Die DNA-Methylierung als epigenetischer Mechanismus der Genregulation könnte eine Quelle geeigneter prognostischer und prädiktiver Biomarker sein.

Material und Methoden

PubMed-Literaturrecherche und eigene Arbeiten.

Ergebnisse

Methylierung von Genen, wie PITX2, ist ein starker, Human Papillomvirus(HPV)-unabhängiger prognostischer Biomarker. Die Methylierung von im Plasma zirkulierender zellfreier DNA von SHOX2 und SEPT9 korreliert mit dem Tumorstadium und der Prognose. Die Methylierung verschiedener Immuncheckpoints, beispielsweise von PD‑1, PD-L1 und CTLA4, ist ebenfalls prognostisch und mit der Genexpression korreliert.

Schlussfolgerungen

Die DNA-Methylierung ist eine Quelle leistungsstarker prognostischer Plasma- und Gewebe-Biomarker, jedoch muss vor einem klinischen Einsatz noch in Studien gezeigt werden, dass eine anhand von Biomarkern gesteuerte Therapiewahl zu einem verbesserten Überleben oder einer Reduzierung der Nebenwirkungen führt. Eine Eignung der DNA-Methylierung als prädiktiver Biomarker für eine zielgerichtete medikamentöse Tumortherapie erscheint vielversprechend, ist jedoch noch nicht ausreichend belegt.

Abstract

Background

Prognostic and predictive biomarkers for personalized treatment management in head and neck squamous cell carcinoma (HNSCC) are of great clinical interest.

Objective

DNA methylation is an epigenetic process involved in gene regulation and could be a source of potential prognostic and predictive biomarkers.

Methods

This study comprises literature research in PubMed and own studies.

Results

Gene methylation, e.g. of PITX2, is a strong, human papillomavirus (HPV)-independent prognostic biomarker. SHOX2 and SEPT9 methylation in circulating cell-free DNA within blood plasma correlates with tumor stage and prognosis. Methylation of diverse immune checkpoints, e.g., PD‑1, PD-L1, and CTLA4, is also prognostic and correlates with gene expression.

Conclusion

DNA methylation is a source of efficient prognostic blood plasma- and tissue-based biomarkers. However, prior to clinical implementation, studies must prove that biomarker-guided treatment selection can lead to better outcomes or reduced toxicity. The applicability of DNA methylation as a predictive biomarker for targeted drug-based cancer therapy seems promising, although further validation is needed.

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Authors and Affiliations

  1. Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum Bonn, Venusberg-Campus 1, 53127, Bonn, Deutschland

    A. Franzen, F. Bootz &  D. Dietrich

Authors
  1. A. Franzen
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  2. F. Bootz
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  3. D. Dietrich
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Corresponding author

Correspondence to D. Dietrich.

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Interessenkonflikt

D. Dietrich besitzt an die Qiagen GmbH auslizenzierte Patente über die Verwendung der DNA-Methylierung von Immuncheckpoint-Genen zur Prädiktion des Ansprechens auf Immuntherapien. A. Franzen und F. Bootz geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Franzen, A., Bootz, F. & Dietrich, D. Prognostische und prädiktive Methylierungsbiomarker für HNSCC. HNO 68, 911–915 (2020). https://doi.org/10.1007/s00106-020-00902-4

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  • DOI: https://doi.org/10.1007/s00106-020-00902-4

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