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

被引:68
作者
Bergheim, Julia [1 ]
Semaan, Alexander [2 ]
Gevensleben, Heidrun [3 ]
Groening, Susanne [4 ]
Knoblich, Andreas [4 ]
Dietrich, Joern [1 ]
Weber, Julia [4 ]
Kalff, Joerg C. [2 ]
Bootz, Friedrich [1 ,3 ]
Kristiansen, Glen
Dietrich, Dimo [1 ]
机构
[1] Univ Hosp Bonn, Dept Otolaryngol Head & Neck Surg, Bonn, Germany
[2] Univ Hosp Bonn, Dept Gen Visceral Thorac & Vasc Surg, Bonn, Germany
[3] Univ Hosp Bonn, Inst Pathol, Bonn, Germany
[4] Marien Hosp Bonn, Dept Visceral Surg, Bonn, Germany
关键词
CARCINOEMBRYONIC ANTIGEN LEVELS; COLON-CANCER; LIVER METASTASES; TUMOR-MARKERS; DIAGNOSIS; BLOOD; PERFORMANCE; ASSAY; CHEMOTHERAPY; PROGNOSIS;
D O I
10.1038/s41416-018-0035-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1217 / 1228
页数:12
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