Department of Geriatric, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, P. R. China.
Department of Thoracic Surgery, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, P. R. China.
Medicine (Baltimore). 2023 Aug 25;102(34):e34860. doi: 10.1097/MD.0000000000034860.
The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. 5-methylcytosine (5mC), a vital DNA methylation marker, plays important roles in gene expression, genomic imprinting, and transposon inhibition. This study aimed to identify the predictors of colon cancer prognosis and lay the foundation for research on therapeutic targets by detecting the levels of 5mC, 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) in colon cancer and adjacent non-tumor tissues. A tissue microarray including 100 colon cancer tissue samples and 60 adjacent non-tumor tissue samples was used. The expression levels of 5mC and its ramifications were assessed by immunohistochemistry. According to the expression levels, patients were divided into moderately positive and strongly positive groups, and the correlation between clinicopathological characteristics and methylation marks was assessed using 2-sided chi-square tests. The prognostic values of 5mC, 5hmC, 5fC, and 5caC were tested using Kaplan-Meier analyses. Compared with adjacent non-tumor tissues, the overall levels of DNA methylation were lower in colon carcinoma lesions. However, the clinical parameters were not significantly associated with these methylation markers, except for 5hmC, which was associated with the age of cancer patients (P value = .043). Kaplan-Meier analysis disclosed that moderate positive group had a significantly shorter disease specific survival than strong positive group for patients with different levels of 5mC (65.2 vs 95.2 months, P = .014) and 5hmC (71.2 vs 97.5 months, P = .045). 5mC and its ramifications (5hmC, 5fC, and 5caC) can serve as biomarkers for colon cancer. 5mC and 5hmC are stable predictors and therapeutic targets in colon cancer. However, further understanding of its function will help to reveal the complex tumorigenic process and identify new therapeutic strategies.
结肠癌的发病率和死亡率正在上升，但其诊断的有效生物标志物有限。5-甲基胞嘧啶（5mC）是一种重要的 DNA 甲基化标志物，在基因表达、基因组印迹和转座子抑制中发挥重要作用。本研究旨在通过检测结肠癌和相邻非肿瘤组织中 5mC、5-羟甲基胞嘧啶（5hmC）、5-甲酰基胞嘧啶（5fC）和 5-羧基胞嘧啶（5caC）的水平，鉴定结肠癌预后的预测因子，并为治疗靶点的研究奠定基础。使用包含 100 例结肠癌组织样本和 60 例相邻非肿瘤组织样本的组织微阵列。通过免疫组织化学评估 5mC 及其衍生物的表达水平。根据表达水平，将患者分为中度阳性和强阳性组，并使用双侧 χ2 检验评估临床病理特征与甲基化标记之间的相关性。使用 Kaplan-Meier 分析测试 5mC、5hmC、5fC 和 5caC 的预后价值。与相邻非肿瘤组织相比，结肠癌病变中的总体 DNA 甲基化水平较低。然而，这些甲基化标记物与临床参数之间没有显著相关性，除了 5hmC 与癌症患者的年龄相关（P 值=.043）。Kaplan-Meier 分析显示，5mC 水平不同的患者中，中度阳性组的疾病特异性生存率明显短于强阳性组（65.2 与 95.2 个月，P=.014）和 5hmC 水平不同的患者（71.2 与 97.5 个月，P=.045）。5mC 及其衍生物（5hmC、5fC 和 5caC）可以作为结肠癌的生物标志物。5mC 和 5hmC 是结肠癌稳定的预测因子和治疗靶点。然而，进一步了解其功能将有助于揭示复杂的肿瘤发生过程，并确定新的治疗策略。
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