Potential of quantitative SEPT9 and SHOX2 methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study.

Autor: Bergheim J; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany., Semaan A; Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany., Gevensleben H; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Groening S; Department of Visceral Surgery, Marien-Hospital Bonn, Bonn, Germany., Knoblich A; Department of Visceral Surgery, Marien-Hospital Bonn, Bonn, Germany., Dietrich J; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany., Weber J; Department of Visceral Surgery, Marien-Hospital Bonn, Bonn, Germany., Kalff JC; Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany., Bootz F; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany., Kristiansen G; Institute of Pathology, University Hospital Bonn, Bonn, Germany., Dietrich D; Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany. dimo.dietrich@gmail.com.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2018 May; Vol. 118 (9), pp. 1217-1228. Date of Electronic Publication: 2018 Apr 03.
DOI: 10.1038/s41416-018-0035-8
Abstrakt: Background: Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) methylation in circulating cell-free DNA (ccfDNA) are powerful biomarkers for colorectal cancer (CRC) screening, as well as head and neck squamous cell carcinoma staging and monitoring. In the present study, we investigated SEPT9 and SHOX2 ccfDNA methylation as auxiliary pre and post-therapeutic staging parameters in CRC patients.
Methods: ccfDNA methylation was quantified in 184 prospectively enrolled patients prior to and 3-10 days after surgery, and biomarker levels were associated with clinico-pathological parameters.
Results: Pre-therapeutic levels of SHOX2 and SEPT9 ccfDNA methylation were strongly associated with Union for International Cancer Control (UICC) stages, tumour (T), nodal (N), and metastasis (M) categories, and histological grade (all P ≤ 0.001), as well as lymphatic invasion and extracapsular lymph node extension (all P< 0.05). Post-therapeutic SHOX2 and SEPT9 ccfDNA methylation levels correlated with UICC stage (all P  <0.01). SEPT9 ccfDNA methylation further allowed for an accurate pre- and post-therapeutic detection of distant metastases (AUC pre-therapeutic  = 0.79 (95%CI 0.69-0.89), AUC post-therapeutic  = 0.93 (95% CI 0.79-1.0)).
Conclusions: DNA methylation analysis in plasma is a powerful pre and post-therapeutic diagnostic tool for CRC and may add valuable information to current TNM staging, thereby holding the potential to assist in the development of individually tailored treatment protocols.
Databáze: MEDLINE