Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.
Int J Mol Sci. 2022 Sep 6;23(18):10225. doi: 10.3390/ijms231810225.
The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of and at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar's test were used for group comparisons, and Kaplan-Meier curves and a log-rank test were used for prediction. The hypermethylation of at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38-7.73 for RFS, HR = 2.35 and 95% CI = 1.17-4.71 for PFS, HR = 4.32 and 95% CI = 1.8-10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07-5.08 for RFS, HR = 2.42 and 95% CI = 1.19-4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of and at specific loci can be employed for the prognosis of patients with CRC.
原发性肿瘤组织和相邻无肿瘤组织中的 DNA 甲基化状态与侵袭性结直肠癌 (CRC) 的发生有关,并可在早期为个性化癌症治疗提供帮助。从 208 例 CRC 患者中提取肿瘤组织和匹配的相邻非肿瘤组织,使用 MassARRAY 系统检测平台确定特定 CpG 位点处 和 的甲基化水平与 CRC 预后因素之间的相关性。使用 Wilcoxon 符号秩检验、卡方检验和 McNemar 检验进行组间比较,使用 Kaplan-Meier 曲线和对数秩检验进行预测。肿瘤组织中 CpG_4、CpG_5、CpG_15 和 CpG_17 位点 的 异常高甲基化与较短的无复发生存期 (RFS)、无进展生存期 (PFS) 和总生存期 (OS) 显著相关 [风险比 (HR) = 3.26,95%置信区间 (CI) = 1.38-7.73 用于 RFS,HR = 2.35 和 95% CI = 1.17-4.71 用于 PFS,HR = 4.32 和 95% CI = 1.8-10.5 用于 OS]。相比之下,正常组织中 CpG_5 位点 甲基化增加与 RFS 和 PFS 显著延长相关 [HR = 2.33,95% CI = 1.07-5.08 用于 RFS,HR = 2.42 和 95% CI = 1.19-4.91 用于 PFS]。特定 CpG 位点的异常甲基化表明组织具有侵袭性行为。因此,特定基因座上 的差异甲基化可以用于预测 CRC 患者的预后。