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DOI: 10.1055/s-0043-1767211
Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma Patients by Circulating Cell-Free SEPT9 DNA Methylation in Blood
Head and neck squamous cell carcinoma (HNSCC) still frequently recurs and metastasizes resulting in poor five-years overall survival rates. Currently, a gold standard for post-surgical minimal residual disease (MRD) detection in HNSCC patients treated with curative intent is missing. Tumor-derived circulation cell-free DNA (ccfDNA) methylation of septin 9 (SEPT9) in blood plasma is known to be a powerful and minimally invasive biomarker for colorectal cancer screening and staging as well as HNSCC staging and monitoring. We applied quasi-digital methylation-specific real-time PCR to quantify SEPT9 ccfDNA methylation levels 2–30 days post-surgically in plasma from >200 prospectively enrolled HNSCC patients. We used Kaplan-Meier and Cox proportional hazards analyses for univariate, pairwise bivariate, and multivariate analyses of disease-free survival in patients stratified by post-surgical SEPT9 ccfDNA methylation positivity. We were able to show that post-surgical SEPT9 cffDNA methylation positivity in blood plasma is a significant independent prognostic factor after statistical analysis regarding AJCC/UICC tumor stage. Thus SEPT9 circulating cell-free DNA methylation in blood is a powerful minimally invasive biomarker for post-surgical residual disease associated with poor outcome. Patients with post-surgically positive SEPT9 cffDNA methylation test results are at high risk of disease recurrence and might benefit from an intensified adjuvant treatment and surveillance.
BONFOR Forschungsförderprogramm der Medizinischen Fakultät der Rheinischen Friedrich Wilhelms-Universität Bonn
Publikationsverlauf
Artikel online veröffentlicht:
12. Mai 2023
Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany