外周 T 细胞中乳腺癌的 DNA 甲基化特征。
DNA methylation signatures of breast cancer in peripheral T-cells.
机构信息
Department of Medicine, McGill University Health Center, 1001 Décarie Blvd., Room EM1.3232, Montréal, QC, H4A3J1, Canada.
Department of Pharmacology and Therapeutics, McGill University Health Center, Montreal, QC, Canada.
出版信息
BMC Cancer. 2018 May 18;18(1):574. doi: 10.1186/s12885-018-4482-7.
BACKGROUND
Immune surveillance acts as a defense mechanism in cancer, and its disruption is involved in cancer progression. DNA methylation reflects the phenotypic identity of cells and recent data suggested that DNA methylation profiles of T cells and peripheral blood mononuclear cells (PBMC) are altered in cancer progression.
METHODS
We enrolled 19 females with stage 1 and 2, nine with stage 3 and 4 and 9 age matched healthy women. T cells were isolated from peripheral blood and extracted DNA was subjected to Illumina 450 K DNA methylation array analysis. Raw data was analyzed by BMIQ, ChAMP and ComBat followed by validation of identified genes by pyrosequencing.
RESULTS
Analysis of data revealed ~ 10,000 sites that correlated with breast cancer progression and established a list of 89 CG sites that were highly correlated (p < 0.01, r > 0.7, r < - 0.7) with breast cancer progression. The vast majority of these sites were hypomethylated and enriched in genes with functions in the immune system.
CONCLUSIONS
The study points to the possibility of using DNA methylation signatures as a noninvasive method for early detection of breast cancer and its progression which need to be tested in clinical studies.
背景
免疫监视是癌症的一种防御机制，其功能障碍与癌症的进展有关。DNA 甲基化反映了细胞的表型特征，最近的数据表明，T 细胞和外周血单核细胞（PBMC）的 DNA 甲基化谱在癌症进展中发生改变。
方法
我们招募了 19 名 1 期和 2 期、9 名 3 期和 4 期以及 9 名年龄匹配的健康女性。从外周血中分离 T 细胞，提取 DNA 进行 Illumina 450K DNA 甲基化阵列分析。原始数据经过 BMIQ、ChAMP 和 ComBat 分析，然后通过焦磷酸测序验证鉴定基因。
结果
数据分析显示，约有 10000 个位点与乳腺癌的进展相关，并确定了 89 个 CG 位点与乳腺癌的进展高度相关（p<0.01，r>0.7，r<-0.7）。这些位点绝大多数呈低甲基化状态，富集在与免疫系统功能相关的基因中。
结论
该研究表明，使用 DNA 甲基化特征作为非侵入性方法早期检测乳腺癌及其进展是可能的，这需要在临床研究中进行测试。
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