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Construction of a Prognostic Model Based on Methylation-Related Genes in Patients with Colon Adenocarcinoma
Cancer Management and Research ( IF 3.3 ) Pub Date : 2023-10-05 , DOI: 10.2147/cmar.s417897 ZhenDong Liu 1 , YuYang Xu 1 , Shan Jin 2 , Xin Liu 1 , BaoChun Wang 1
Cancer Management and Research ( IF 3.3 ) Pub Date : 2023-10-05 , DOI: 10.2147/cmar.s417897 ZhenDong Liu 1 , YuYang Xu 1 , Shan Jin 2 , Xin Liu 1 , BaoChun Wang 1
Affiliation
Purpose: Colon adenocarcinoma (COAD) is the second leading cause of death in the world, and the new incidence rate ranks third among all cancers. Abnormal DNA methylation is related to the occurrence and development of tumors. In this study, we aimed to identify genes associated with abnormal methylation in COAD.
Methods: COAD transcriptome data, methylation data and clinical information were downloaded from the TCGA database and GEO database. The differentially expressed genes (DEGs) and methylated genes (DMGs) were analyzed and identified in COAD. PCA analysis was applied to divide COAD into subtypes, and the survival and immune cell infiltration of each subtype were evaluated. Cox and LASSO analyses were performed to construct COAD risk model. GSEA was used to evaluate the enrichment pathways. The Kaplan–Meier was used to analyze the difference in survival. ROC curve was plotted to evaluate the accuracy of the model, and GSE17536 was used to verify the accuracy of the risk model. The risk model is combined with the clinicopathological characteristics of COAD patients to perform multivariate Cox regression analysis to obtain independent risk factors and draw nomograms.
Results: In total, 4564 DEGs and 1093 DMGs were screened, among which 298 were found to be overlapping genes. For 220 of these overlapping genes, the methylation was significantly negatively correlated to expression levels. An optimal signature from 4 methylated biomarkers was identified to construct the prognostic model.
Conclusion: Our study identified 4 methylated biomarkers in the COAD. Then, we constructed the risk model to provide a theoretical basis and reference value for the research and treatment of COAD.
Keywords: colorectal cancer, methylated genes, immune cell infiltration, WGCNA, prognosis
中文翻译：
基于甲基化相关基因的结肠腺癌预后模型构建
目的：结肠腺癌（COAD）是全球第二大死因，新发病率在所有癌症中排名第三。DNA甲基化异常与肿瘤的发生、发展有关。在这项研究中，我们的目的是鉴定与 COAD 异常甲基化相关的基因。
方法：从TCGA数据库和GEO数据库下载COAD转录组数据、甲基化数据和临床信息。在 COAD 中分析和鉴定差异表达基因 (DEG) 和甲基化基因 (DMG)。应用PCA分析将COAD分为亚型，并评估每个亚型的存活和免疫细胞浸润。进行 Cox 和 LASSO 分析来构建 COAD 风险模型。GSEA 用于评估富集途径。Kaplan-Meier 用于分析生存差异。绘制ROC曲线评估模型的准确性，并使用GSE17536验证风险模型的准确性。风险模型结合COAD患者的临床病理特征进行多因素Cox回归分析，获得独立危险因素并绘制列线图。
结果：共筛选出4564个DEG和1093个DMG，其中发现298个重叠基因。对于其中 220 个重叠基因，甲基化与表达水平显着负相关。确定了 4 个甲基化生物标志物的最佳特征以构建预后模型。
结论：我们的研究在 COAD 中鉴定出了 4 个甲基化生物标志物。然后构建风险模型，为COAD的研究和治疗提供理论依据和参考价值。
关键词:结直肠癌, 甲基化基因, 免疫细胞浸润, WGCNA, 预后
更新日期：2023-10-05
Methods: COAD transcriptome data, methylation data and clinical information were downloaded from the TCGA database and GEO database. The differentially expressed genes (DEGs) and methylated genes (DMGs) were analyzed and identified in COAD. PCA analysis was applied to divide COAD into subtypes, and the survival and immune cell infiltration of each subtype were evaluated. Cox and LASSO analyses were performed to construct COAD risk model. GSEA was used to evaluate the enrichment pathways. The Kaplan–Meier was used to analyze the difference in survival. ROC curve was plotted to evaluate the accuracy of the model, and GSE17536 was used to verify the accuracy of the risk model. The risk model is combined with the clinicopathological characteristics of COAD patients to perform multivariate Cox regression analysis to obtain independent risk factors and draw nomograms.
Results: In total, 4564 DEGs and 1093 DMGs were screened, among which 298 were found to be overlapping genes. For 220 of these overlapping genes, the methylation was significantly negatively correlated to expression levels. An optimal signature from 4 methylated biomarkers was identified to construct the prognostic model.
Conclusion: Our study identified 4 methylated biomarkers in the COAD. Then, we constructed the risk model to provide a theoretical basis and reference value for the research and treatment of COAD.
Keywords: colorectal cancer, methylated genes, immune cell infiltration, WGCNA, prognosis
中文翻译：
基于甲基化相关基因的结肠腺癌预后模型构建
目的：结肠腺癌（COAD）是全球第二大死因，新发病率在所有癌症中排名第三。DNA甲基化异常与肿瘤的发生、发展有关。在这项研究中，我们的目的是鉴定与 COAD 异常甲基化相关的基因。
方法：从TCGA数据库和GEO数据库下载COAD转录组数据、甲基化数据和临床信息。在 COAD 中分析和鉴定差异表达基因 (DEG) 和甲基化基因 (DMG)。应用PCA分析将COAD分为亚型，并评估每个亚型的存活和免疫细胞浸润。进行 Cox 和 LASSO 分析来构建 COAD 风险模型。GSEA 用于评估富集途径。Kaplan-Meier 用于分析生存差异。绘制ROC曲线评估模型的准确性，并使用GSE17536验证风险模型的准确性。风险模型结合COAD患者的临床病理特征进行多因素Cox回归分析，获得独立危险因素并绘制列线图。
结果：共筛选出4564个DEG和1093个DMG，其中发现298个重叠基因。对于其中 220 个重叠基因，甲基化与表达水平显着负相关。确定了 4 个甲基化生物标志物的最佳特征以构建预后模型。
结论：我们的研究在 COAD 中鉴定出了 4 个甲基化生物标志物。然后构建风险模型，为COAD的研究和治疗提供理论依据和参考价值。
关键词:结直肠癌, 甲基化基因, 免疫细胞浸润, WGCNA, 预后
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