口腔鳞状细胞癌中 DNA 甲基化谱的术前评估可预测肿瘤侵袭潜能。
Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential.
机构信息
Section of Oral Science, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40159 Bologna, Italy.
Section of Anatomic Pathology at Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
出版信息
Int J Mol Sci. 2020 Sep 14;21(18):6691. doi: 10.3390/ijms21186691.
BACKGROUND
Prognosis of oral squamous cell carcinoma (OSCC) is difficult to exactly assess on pre-operative biopsies. Since OSCC DNA methylation profile has proved to be a useful pre-operative diagnostic tool, the aim of the present study was to evaluate the prognostic impact of DNA methylation profile to discriminate OSCC with high and low aggressive potential.
METHODS
36 OSCC cases underwent neoplastic cells collection by gentle brushing of the lesion, before performing a pre-operative biopsy. The CpG islands methylation status of 13 gene (, , , , , , , , , , , , ) was studied by bisulfite Next Generation Sequencing (NGS). A Cox proportional hazards model via likelihood-based component-wise boosting was used to evaluate the prognostic power of the CpG sites.
RESULTS
The boosting estimation identified five CpGs with prognostic significance: , , , and . The combination of significant provided promising results for adverse events prediction (Brier score = 0.080, C-index = 0.802 and AUC = 0.850). had a strong prognostic power in patients with early OSCC.
CONCLUSIONS
These data confirm that the study of methylation profile provides new insights into the molecular mechanisms of OSCC and can allow a better OSCC prognostic stratification even before surgery.
背景
口腔鳞状细胞癌（OSCC）的预后很难通过术前活检准确评估。由于 OSCC 的 DNA 甲基化图谱已被证明是一种有用的术前诊断工具，因此本研究旨在评估 DNA 甲基化图谱对区分具有高侵袭性和低侵袭性潜能的 OSCC 的预后影响。
方法
36 例 OSCC 患者在进行术前活检前，通过轻轻刷洗病变部位采集肿瘤细胞。通过亚硫酸氢盐二代测序（NGS）研究了 13 个基因（,,,,,,,,,,,,, ）的 CpG 岛甲基化状态。通过基于似然的组件逐步提升的 Cox 比例风险模型评估 CpG 位点的预后能力。
结果
提升估计确定了五个具有预后意义的 CpG：,,, 和 。显著的 组合为不良事件预测提供了有前景的结果（Brier 评分=0.080，C 指数=0.802，AUC=0.850）。在早期 OSCC 患者中， 具有很强的预后能力。
结论
这些数据证实，对甲基化图谱的研究为 OSCC 的分子机制提供了新的见解，并可以在术前甚至更好地对 OSCC 进行预后分层。
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