Department of Population and Quantitative Health Sciences, Institute of Computational Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Department of Family Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia.
Cancer Epidemiol Biomarkers Prev. 2019 Oct;28(10):1720-1724. doi: 10.1158/1055-9965.EPI-19-0208. Epub 2019 Aug 2.
Epigenetic clock, or DNA methylation age, has been shown to highly correlate with chronologic age. Epigenetic age acceleration, the difference between DNA methylation age and individual's chronologic age, was observed in colorectal cancer. However, the association of epigenetic age acceleration with colorectal cancer tumor molecular characteristics, clinical characteristics, and patient outcomes has not been systematically investigated.
DNA methylation ages of 345 patients with colorectal cancer from The Cancer Genome Atlas (TCGA) were computed using the Horvath age prediction model. Multivariate linear regression was used to assess the association of epigenetic age acceleration with molecular and clinical features of colorectal cancer, including consensus molecular subtypes (CMS1-CMS4) and tumor stage Cox proportional hazards regression was used to assess the association of epigenetic age acceleration with survival.
Epigenetic age acceleration is significantly associated with CMS. Compared with CMS2, epigenetic age acceleration for CMS1, CMS3, and CMS4 was 23.90 years [ = 5.55E-11; 95% confidence interval (CI): 17.10-30.69], 9.16 years ( = 5.84E-03; 95% CI: 2.68-15.65), and 6.05 years ( = 2.69E-02; 95% CI: 0.70-11.41), respectively. Furthermore, epigenetic age acceleration is statistically significantly and positively associated with total mortality (HR = 1.97; 95% CI: 1.14-3.39; = 0.014).
Epigenetic age acceleration is associated with colorectal cancer tumor molecular characteristics, and a significant predictor of overall survival of colorectal cancer, along with age and tumor stage.
Combining information of colonic tissue epigenetic age acceleration and tumor molecular characteristics may improve prognosis prediction in colorectal cancer.
表观遗传时钟或 DNA 甲基化年龄与实际年龄高度相关。在结直肠癌中观察到表观遗传年龄加速，即 DNA 甲基化年龄与个体实际年龄之间的差异。然而，表观遗传年龄加速与结直肠癌肿瘤分子特征、临床特征和患者预后的关系尚未得到系统研究。
使用 Horvath 年龄预测模型计算了来自癌症基因组图谱（TCGA）的 345 例结直肠癌患者的 DNA 甲基化年龄。使用多元线性回归评估了表观遗传年龄加速与结直肠癌的分子和临床特征的关系，包括共识分子亚型（CMS1-CMS4）和肿瘤分期 Cox 比例风险回归用于评估表观遗传年龄加速与生存的关系。
表观遗传年龄加速与 CMS 显著相关。与 CMS2 相比，CMS1、CMS3 和 CMS4 的表观遗传年龄加速分别为 23.90 岁[=5.55E-11；95%置信区间（CI）：17.10-30.69]、9.16 岁（=5.84E-03；95% CI：2.68-15.65）和 6.05 岁（=2.69E-02；95% CI：0.70-11.41）。此外，表观遗传年龄加速与总死亡率呈统计学显著正相关（HR=1.97；95%CI：1.14-3.39；=0.014）。
表观遗传年龄加速与结直肠癌肿瘤分子特征相关，是结直肠癌总生存的重要预测指标，与年龄和肿瘤分期相关。
结合结直肠组织表观遗传年龄加速和肿瘤分子特征的信息可能会改善结直肠癌的预后预测。
