研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

5-甲基胞苷(5mC)的缺乏与结直肠癌的发生和预后的关系。

The deficiency of 5-methylcytosine (5mC) and its ramification in the occurrence and prognosis of colon cancer.

发表日期:2023 Aug 25
作者: Xin-Xin Yan, Na Guo, Song-Wei Ru, Zhi-Yuan Wang, Hai-Juan Sui, Yin-Shi Xu, Zhen-Dan Yao
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

结直肠癌的发病率和死亡率正在上升,有效的诊断生物标志物有限。5-甲基胞嘧啶(5mC)是一种重要的DNA甲基化标记物,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直肠癌和相邻非肿瘤组织中的5mC、5-羟甲基胞嘧啶(5hmC)、5-甲酰胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)水平,识别结直肠癌预后的预测因子,并为治疗靶点的研究奠定基础。使用了包括100例结直肠癌组织样本和60例相邻非肿瘤组织样本的组织微阵列。通过免疫组织化学检测评估了5mC及其分枝的表达水平。根据表达水平将患者分为中度阳性组和强阳性组,并使用双侧卡方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分析测试了5mC、5hmC、5fC和5caC的预后价值。与相邻非肿瘤组织相比,结直肠癌病变的DNA甲基化水平较低。然而,临床参数与这些甲基化标记物的相关性没有显著性,除了5hmC与癌症患者年龄相关(P值=0.043)。Kaplan-Meier分析显示,对于不同5mC(65.2 vs 95.2个月,P=0.014)和5hmC水平(71.2 vs 97.5个月,P=0.045)的患者,中度阳性组的特定疾病生存期明显较短。5mC及其分枝(5hmC、5fC和5caC)可以作为结直肠癌的生物标志物。5mC和5hmC是结直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,并找到新的治疗策略。© 2023年作者。 Wolters Kluwer Health, Inc. 发表。
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.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.