Post-surgical SEPT9 Circulating Cell-free DNA Methylation Positivity as a Molecular Staging Parameter in Head and Neck Squamous Cell Cancer Patients

Liquid biopsies allow for the non-invasive detection of tumorous circulating cell-free DNA (ccfDNA) in blood plasma of head and neck squamous cell carcinoma (HNSCC) patients. The current study tested the performance of post-surgical SEPT9 ccfDNA methylation as a molecular staging parameter in HNSCC as adjunct to established prognostic factors. A cohort of n = 219 prospectively enrolled HNSCC patients suffering from localized or locally advanced disease were tested for post-surgical SEPT9 ccfDNA methylation in their blood plasma via quantitative methylation specific real-time PCR. SEPT9 ccfDNA methylation positivity was then correlated with established prognostic factors, namely 8th  edition of AJCC/UICC stage, surgical margin, lymphatic and vascular invasion. Post-surgical SEPT9 DNA methylation positivity was detected in 26.5 % (58/219) of all analyzed cases and is significantly associated with AJCC/UICC stage (P = 0.001), lymphatic invasion (P = 0.032), vascular invasion (P = 0.012), and a histopathologically verified positive surgical margin (P < 0.001) in localized and locally advanced HNSCC.Post-surgical SEPT9 ccfDNA methylation in blood is a promising molecular staging parameter in localized and locally advanced HNSCC patients. Future studies are necessary to evaluate the clinical relevance of post-surgical SEPT9 ccfDNA methylation positivity to personalize patients’ adjuvant treatment.

BONFOR Forschungsförderungsprogramm der Medizinische Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn