基于血清甲基化谱建立结直肠癌肝转移预测模型及预后价值的评价

Early prediction of liver metastases of colorectal cancer is very important in clinical practice, however, there is still lack of effective predictive biomarkers. Our preliminary results demonstrated that the DNA 450K methylation chip was an effective tool for screening the serum methylation profiles. Based on this, we propose a hypothesis: Serum DNA methylation profiles and multi-parameter joint analysis may be used to build a prediction model of liver metastases of colorectal cancer and prognosis evaluation. To test this hypothesis, we used DNA methylation 450K chips, bioinformatic analysis, bisulfite sequencing, multi-parameter joint analysis and prognostic evaluation. From the needs of clinical practice, by methylation chips screening, bioinformatics analysis and multi-parameter analysis methods, and then back to the clinical practice. After this, we completely built a predictive model of liver metastases of colorectal cancer by translational medicine model. In our study, we provide a new predictive model and prognosis indicators for the liver metastases of colorectal cancer based on a new viewpoint of combining the serum DNA methylation profiles and multi-parameter joint analysis.

结直肠癌肝转移的早期预测在临床上尤为重要，然而，临床上尚缺乏有效的预测指标。我们的前期结果证明DNA 450K甲基化芯片是一种有效的血清甲基化谱筛选工具。为此，我们提出假说：血清甲基化谱及多参数联合分析可以建立结直肠癌肝转移的预测模型及预后评价。为了验证这一假说，我们采用DNA 450K甲基化芯片、生物信息学分析、重亚硫酸盐测序、多参数联合分析以及预后评价等手段。从临床需求出发，经芯片筛选、生物信息学分析和多参数分析等多方面研究，最后回归到临床，完成血清甲基化谱用于结直肠癌肝转移预测的转化医学模式。本研究从血清甲基化谱和多参数联合分析这个新视点为结直肠癌肝转移的预测及预后评价提供一种新的模型和评价指标。

结直肠癌肝转移的早期预测在临床上尤为重要，然而，临床上尚缺乏有效的预测指标。我们的前期结果证明DNA 450K甲基化芯片是一种有效的血清甲基化谱筛选工具。我们通过DNA methylation 450K甲基化芯片和生物信息学相结合，筛选可用于结直肠癌肝转移预测的20个甲基化位点。然后通过实时荧光定量PCR技术以及常用的血液学指标和多参数联合分析技术相结合，建立并验证了结直肠癌肝转移的血清甲基化谱预测模型，其诊断灵敏性和特异性分别为93.32%和93.97%。有望为结直肠癌肝转移的预测及预后评价提供一种新的模型和评价指标，为结直肠癌肝转移的防治提供新的思路。项目执行期间发表SCI论文4篇，以本部分研究成果为基础，作为课题负责人和子课题负责人，获得国家重点研发计划（2016YFC0106604）及北京市科技计划（首都健康保障培育研究，Z181100001618015）两项课题的资助。培养硕士研究生2名。