학술논문
Circulating Cell-Free SEPT9 DNA Methylation in Blood Is a Biomarker for Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma Patients.
Document Type
Academic Journal
Author
Dietrich D; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Weider S; Department of Oral and Maxillofacial Surgery, University Medical Center Bonn (UKB), Bonn, Germany.; de Vos L; Department of Dermatology and Allergology, University Medical Center Bonn (UKB), Bonn, Germany.; Vogt TJ; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Färber M; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Zarbl R; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Hunecke A; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Glosch AK; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Gabrielpillai J; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Bootz F; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Bauernfeind FG; Department of Oncology, Hematology and Rheumatology, University Medical Center Bonn (UKB), Bonn, Germany.; Kramer FJ; Department of Oral and Maxillofacial Surgery, University Medical Center Bonn (UKB), Bonn, Germany.; Kristiansen G; Department of Pathology, University Medical Center Bonn (UKB), Bonn, Germany.; Brossart P; Department of Oncology, Hematology and Rheumatology, University Medical Center Bonn (UKB), Bonn, Germany.; Strieth S; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.; Franzen A; Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 9421549 Publication Model: Print Cited Medium: Internet ISSN: 1530-8561 (Electronic) Linking ISSN: 00099147 NLM ISO Abbreviation: Clin Chem Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Tumorous SEPT9 (septin 9, SEPTIN9) circulating cell-free DNA (ccfDNA) methylation in blood plasma is a powerful biomarker for diagnosis, molecular staging, prognosis, and recurrence monitoring in head and neck squamous cell carcinoma (HNSCC) patients. The present study aimed to evaluate the clinical performance of SEPT9 ccfDNA methylation to detect post-surgical minimal residual disease (MRD) in patients with localized or locally advanced HNSCC treated with curative intent.
Methods: We applied quasi-digital methylation-specific real-time PCR to quantify SEPT9 ccfDNA methylation levels 2 to 30 days post-surgically in plasma from n = 219 prospectively enrolled HNSCC patients. We tested the associations of SEPT9 ccfDNA methylation with clinicopathological parameters and used Kaplan-Meier and Cox proportional hazards analyses for univariate, pairwise bivariate, and multivariate analyses of disease-free survival.
Results: Of 219 patients, 26.5% (58/219) were post-surgically SEPT9 ccfDNA methylation positive. SEPT9 ccfDNA methylation positivity was significantly associated with tumor site, American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC; 8th edition) tumor stage, nodal category and extracapsular extension, lymphatic and vascular invasion, and surgical margin. Bivariate Cox proportional hazards analysis proved post-surgical SEPT9 ccfDNA methylation positivity to be an independent prognostic factor tested together with AJCC/UICC tumor stage (SEPT9: hazard ratio [HR] = 2.43, 95% CI, 1.37-4.30, P = 0.002; AJCC/UICC stage: HR = 1.48, 95% CI, 1.11-1.98, P = 0.008).
Conclusions: Post-surgical SEPT9 ccfDNA methylation may aid to identify high-risk HNSCC patients who could benefit from an intensified adjuvant treatment and surveillance.
(© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Methods: We applied quasi-digital methylation-specific real-time PCR to quantify SEPT9 ccfDNA methylation levels 2 to 30 days post-surgically in plasma from n = 219 prospectively enrolled HNSCC patients. We tested the associations of SEPT9 ccfDNA methylation with clinicopathological parameters and used Kaplan-Meier and Cox proportional hazards analyses for univariate, pairwise bivariate, and multivariate analyses of disease-free survival.
Results: Of 219 patients, 26.5% (58/219) were post-surgically SEPT9 ccfDNA methylation positive. SEPT9 ccfDNA methylation positivity was significantly associated with tumor site, American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC; 8th edition) tumor stage, nodal category and extracapsular extension, lymphatic and vascular invasion, and surgical margin. Bivariate Cox proportional hazards analysis proved post-surgical SEPT9 ccfDNA methylation positivity to be an independent prognostic factor tested together with AJCC/UICC tumor stage (SEPT9: hazard ratio [HR] = 2.43, 95% CI, 1.37-4.30, P = 0.002; AJCC/UICC stage: HR = 1.48, 95% CI, 1.11-1.98, P = 0.008).
Conclusions: Post-surgical SEPT9 ccfDNA methylation may aid to identify high-risk HNSCC patients who could benefit from an intensified adjuvant treatment and surveillance.
(© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)