British journal of cancer · 2018
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.
СтатьяНаблюдательное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bergheim Julia, Semaan Alexander, Gevensleben Heidrun, Groening Susanne, Knoblich Andreas, Dietrich Jörn, Weber Julia, Kalff Jörg C, Bootz Friedrich, Kristiansen Glen, Dietrich Dimo
Аннотация
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 (AUCpre-therapeutic = 0.79 (95%CI 0.69-0.89), AUCpost-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.
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 (AUCpre-therapeutic = 0.79 (95%CI 0.69-0.89), AUCpost-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.