Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn, Bonn, Germany.
Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany.
Br J Cancer. 2018 May;118(9):1217-1228. doi: 10.1038/s41416-018-0035-8. Epub 2018 Apr 3.
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.
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.
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 = 0.79 (95%CI 0.69-0.89), AUC = 0.93 (95% CI 0.79-1.0)).
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.
循环无细胞 DNA（ccfDNA）中的 Septin9（SEPT9）和矮小同源盒 2（SHOX2）甲基化是结直肠癌（CRC）筛查以及头颈部鳞状细胞癌分期和监测的强大生物标志物。在本研究中，我们研究了 SEPT9 和 SHOX2 ccfDNA 甲基化为 CRC 患者辅助治疗前和治疗后分期的参数。
前瞻性纳入 184 例患者，在手术前和术后 3-10 天内定量检测 ccfDNA 甲基化，分析生物标志物水平与临床病理参数的相关性。
治疗前 SHOX2 和 SEPT9 ccfDNA 甲基化水平与国际抗癌联盟（UICC）分期、肿瘤（T）、淋巴结（N）和转移（M）分期以及组织学分级均密切相关（均 P≤0.001），并且与淋巴管浸润和包膜外淋巴结转移相关（均 P<0.05）。治疗后 SHOX2 和 SEPT9 ccfDNA 甲基化水平与 UICC 分期相关（均 P<0.01）。SEPT9 ccfDNA 甲基化可准确检测治疗前后的远处转移（AUC=0.79（95%CI 0.69-0.89），AUC=0.93（95%CI 0.79-1.0））。
血浆中的 DNA 甲基化分析是 CRC 治疗前和治疗后的强大诊断工具，它可能为当前的 TNM 分期提供有价值的信息，从而有可能辅助制定个体化的治疗方案。
