This study aimed to identify prognostic epigenetic biomarkers for colon cancer (CC). Methylation and mRNA expression in CC samples with clinical characteristics that corresponded to those in The Cancer Genome Atlas were analyzed. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were screened between matched tumor and nontumor tissues. Among the 415 DEGs and DMGs that significantly correlated between cytosine-phosphate-guanine (CpG) methylation and gene expression, unc-5 netrin receptor C (UNC5C), solute carrier family 35 member F (SLC35F)1, Ly6/Neurotoxin (LYNX)1, stathmin (STMN)2, slit guidance ligand (SLIT)3, cell adhesion molecule L1 like (CHL1), CAP-Gly domain containing linker protein family member 4 (CLIP4), transmembrane protein (TMEM) 255A, granzyme B (GZMB), and brain expressed X-Linked (BEX)1 were promising epigenetic biomarkers. Prediction was more accurate when models were based on the expression and/or methylation of GZMB rather than clinical stage. Comparisons of tissues with high or low GZMB expression significantly associated the DEGs with natural killer-mediated cytotoxicity, cytokine–cytokine receptor interactions, and chemokine signaling pathways. From among the 10 epigenetic biomarkers, GZMB might serve as a tumor suppressor and function in several immune-related pathways in CC. Prognostic models based on GZMB expression and/or methylation would be significant for patients with CC.

中文翻译：

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甲基化和表达的基因作为结肠癌的预后表观生物标志物

这项研究旨在确定结肠癌（CC）的预后表观生物标志物。分析了具有与《癌症基因组图谱》相对应的临床特征的CC样本中的甲基化和mRNA表达。在匹配的肿瘤组织和非肿瘤组织之间筛选差异甲基化基因（DMG）和差异表达基因（DEG）。在415个DEG和DMG中，胞嘧啶-磷酸-鸟嘌呤（CpG）甲基化与基因表达显着相关，其中unc-5 netrin受体C（UNC5C），溶质载体家族35成员F（SLC35F）1，Ly6 /神经毒素（LYNX）1，stathmin（STMN）2，狭缝引导配体（SLIT）3，细胞粘附分子L1 like（CHL1），CAP-Gly结构域含有接头蛋白家族4（CLIP4），跨膜蛋白（TMEM）255A，颗粒酶B（GZMB）和脑表达的X连锁（BEX）1是有前途的表观生物标志物。当模型基于GZMB的表达和/或甲基化时，预测更为准确而不是临床阶段。具有高或低GZMB表达的组织的比较将DEGs与自然杀手介导的细胞毒性，细胞因子-细胞因子受体相互作用和趋化因子信号通路密切相关。在这10种表观遗传标志物中，GZMB可能是一种肿瘤抑制因子，并在CC的几种免疫相关途径中起作用。基于GZMB表达和/或甲基化的预后模型对CC患者具有重要意义。