The present study aimed to construct a novel methylation-related prognostic model based on microsatellite status that may enhance the prognosis of colorectal cancer (CRC) from methylation and microsatellite status perspective. DNA methylation and mRNA expression data with clinical information were downloaded from The Cancer Genome Atlas (TCGA) data set. The samples were divided into microsatellite stability and microsatellite instability group, and CIBERSORT was used to assess the immune cell infiltration characteristics. After identifying the differentially methylated genes and differentially expression genes using R packages, the methylation-driven genes were further identified. Prognostic genes that were used to establish the methylation-related risk score model were generated by the univariate and multivariate Cox regression model. Finally, we established and evaluated the methylation-related prognostic model for CRC patients. A total of 69 MDGs were obtained and three of these genes (MIOX, TH, DKFZP434K028) were selected to construct the prognostic model. Patients in the low-risk score group had a conspicuously better overall survival than those in the high-risk score group (p < .0001). The area under the receiver operating characteristic curve for this model was 0.689 at 3 years, 0.674 at 4 years, and 0.658 at 5 years. The Wilcoxon test showed that higher risk score was associated with higher T stage (p = .01), N stages (p = .0028), metastasis (p = .013), and advanced pathological stage (p = .0013). However, the more instability of microsatellite status, the lower risk score of CRC patients (p = .0048). Our constructed methylation-related prognostic model based on microsatellite status presents potential significance in assessing recurrence risk stratification, tumor staging, and immunotherapy for CRC patients.

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基于微卫星状态的结直肠癌甲基化相关预后模型的构建

本研究旨在构建一种基于微卫星状态的新型甲基化相关预后模型，该模型可能从甲基化和微卫星状态的角度提高结直肠癌 (CRC) 的预后。从癌症基因组图谱（TCGA）数据集中下载具有临床信息的 DNA 甲基化和 mRNA 表达数据。将样本分为微卫星稳定组和微卫星不稳定组，采用CIBERSORT评估免疫细胞浸润特性。使用R包鉴定差异甲基化基因和差异表达基因后，进一步鉴定甲基化驱动基因。用于建立甲基化相关风险评分模型的预后基因由单变量和多变量 Cox 回归模型生成。最后，我们建立并评估了 CRC 患者的甲基化相关预后模型。总共获得了 69 个 MDG，其中三个基因（选择MIOX、TH、DKFZP434K028 ) 构建预后模型。低风险评分组患者的总生存期明显优于高风险评分组患者（p  < .0001）。该模型的受试者工作特征曲线下面积在 3 年时为 0.689，在 4 年时为 0.674，在 5 年时为 0.658。Wilcoxon 检验表明，较高的风险评分与较高的 T 分期 ( p  = .01)、N 分期 ( p = .0028)  、转移 ( p  = .013) 和晚期病理分期 ( p  = .0013) 相关。然而，微卫星状态越不稳定，CRC患者的风险评分越低（p = .0048)。我们构建的基于微卫星状态的甲基化相关预后模型在评估 CRC 患者的复发风险分层、肿瘤分期和免疫治疗方面具有潜在意义。