Luo Can, Huang Jiaheng, Guo Zhaoze, Guo Jingyun, Zeng Xiaoqi, Li Yimin, Liu Minfeng
Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.
Ann Transl Med. 2021 Apr;9(8):683. doi: 10.21037/atm-21-1128.
Aberrant methylation is common during the early stage of cancer development. This study was designed to investigate DNA methylation as biomarker for breast cancer.
Public database analysis and methylation-specific whole-gene sequencing were conducted to identify methylated biomarkers that would enable early non-invasive diagnosis of breast cancer. Firstly, the data was obtained from the TCGA Database and the Blueprint Epigenome Database. Secondly, methylation-specific whole-gene sequencing was conducted in 10 female patients with early-stage breast cancer and 10 healthy female volunteers from Nanfang Hospital of Southern Medical University between March 2018 and July 2018. Thirdly, the R language was used for data analysis, and KEGG and DAVID online tool was used for annotations.
We found that methylation levels at 13 cytosine-phosphate-guanine (CpG) sites (cg04066177, cg04281344, cg05995576, cg06221609, cg08642731, cg11388802, cg12665414, cg14557216, cg19404723, cg19457909, cg24570211, cg25818763, and cg26215982) in the malignant tissue DNA were highly comparable to those of circulating cell-free DNA (cfDNA) of breast cancer patients, but were significantly different from those of normal tissue DNA, cfDNA of healthy women, and leukocyte DNA. In addition, three CpG sites (cg04281344, cg24570211, and cg26215982) were confirmed in clinical research, which showed that the sensitivity and specificity of these CpGs as biomarkers for breast cancer were 69.4-83.7% and 85.7-88.6%, respectively.
New biomarkers were identified and confirmed for breast cancer by comparing the methylation of tumour tissues, leukocytes, and non-plasma DNA.
异常甲基化在癌症发展的早期阶段很常见。本研究旨在调查DNA甲基化作为乳腺癌生物标志物的情况。
进行公共数据库分析和甲基化特异性全基因测序，以鉴定能够实现乳腺癌早期非侵入性诊断的甲基化生物标志物。首先，数据来自TCGA数据库和蓝图表观基因组数据库。其次，于2018年3月至2018年7月在南方医科大学南方医院对10例早期乳腺癌女性患者和10名健康女性志愿者进行甲基化特异性全基因测序。第三，使用R语言进行数据分析，并使用KEGG和DAVID在线工具进行注释。
我们发现，恶性组织DNA中13个胞嘧啶-磷酸-鸟嘌呤（CpG）位点（cg04066177、cg04281344、cg05995576、cg06221609、cg08642731、cg11388802、cg12665414、cg14557216、cg19404723、cg19457909、cg24570211、cg25818763和cg26215982）的甲基化水平与乳腺癌患者循环游离DNA（cfDNA）的甲基化水平高度可比，但与正常组织DNA、健康女性cfDNA和白细胞DNA的甲基化水平有显著差异。此外，临床研究证实了3个CpG位点（cg04281344、cg24570211和cg26215982），结果显示这些CpG作为乳腺癌生物标志物的敏感性和特异性分别为69.4 - 83.7%和85.7 - 88.6%。
通过比较肿瘤组织、白细胞和非血浆DNA的甲基化情况，鉴定并确认了新的乳腺癌生物标志物。
