A multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer

被引：32

作者：

Wang, Tiantian ^{[1
]}

Li, Peilong ^{[1
]}

Qi, Qiuchen ^{[1
]}

Zhang, Shujun ^{[1
]}

Xie, Yan ^{[1
]}

Wang, Jing ^{[1
]}

Liu, Shibiao ^{[1
]}

Ma, Suhong ^{[1
]}

Li, Shijun ^{[2
]}

Gong, Tingting ^{[3
]}

Xu, Huiting ^{[4
,5
]}

Xiong, Mengqiu ^{[6
]}

Li, Guanghua ^{[7
]}

You, Chongge ^{[8
]}

Luo, Zhaofan ^{[9
]}

Li, Juan ^{[1
]}

Du, Lutao ^{[1
,10
]}

Wang, Chuanxin ^{[1
,11
,12
]}

机构：

[1] Shandong Univ, Hosp 2, Dept Clin Lab, 247 Beiyuan St, Jinan 250033, Shandong, Peoples R China

[2] Dalian Med Univ, Hosp 1, Clin Lab, Dalian 116011, Peoples R China

[3] Anhui Med Univ, Affiliated Hosp 1, Clin Lab, Hefei 230022, Peoples R China

[4] Nantong Univ, Affiliated Tumor Hosp, Dept Clin Lab Med, Nantong 226361, Jiangsu, Peoples R China

[5] Nantong Univ, Med Sch, Nantong 226001, Peoples R China

[6] Nanjing Med Univ, Nanjing Hosp 1, Clin Lab, Nanjing 210006, Peoples R China

[7] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Clin Lab, Guangzhou 510000, Peoples R China

[8] Lanzhou Univ, Hosp 2, Clin Med Coll 2, Lab Med Ctr, Lanzhou 730000, Peoples R China

[9] Sun Yat Sen Univ, Affiliated Hosp 7, Dept Clin Lab, Shenzhen 518107, Peoples R China

[10] Shandong Univ, Qilu Hosp, Dept Clin Lab, Shandong Prov Key Lab Innovat Technol Lab Med, Jinan 250012, Peoples R China

[11] Shandong Engn & Technol Res Ctr Tumor Marker Dete, Jinan 250033, Peoples R China

[12] Shandong Prov Clin Med Res Ctr, Clin Lab, Jinan 250033, Peoples R China

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SERUM TUMOR-MARKERS; CELLS; HYPOMETHYLATION; IDENTIFICATION; EXPRESSION; MORTALITY; DIAGNOSIS; BIOMARKER; HARMS; POWER;

D O I：

10.1038/s41467-023-40389-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The immune system can monitor tumor development, and DNA methylation is involved in the body's immune response to tumors. In this work, we investigate whether DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) could be used as markers for early detection of breast cancer (BC) from the perspective of tumor immune alterations. We identify four BC-specific methylation markers by combining Infinium 850 K BeadChips, pyrosequencing and targeted bisulfite sequencing. Based on the four methylation markers in PBMCs of BC, we develop an efficient and convenient multiplex methylation-specific quantitative PCR assay for the detection of BC and validate its diagnostic performance in a multicenter cohort. This assay was able to distinguish early-stage BC patients from normal controls, with an AUC of 0.940, sensitivity of 93.2%, and specificity of 90.4%. More importantly, this assay outperformed existing clinical diagnostic methods, especially in the detection of early-stage and minimal tumors. DNA methylation pattern of immune cells can be altered during tumour development. Here, the authors identify 4 DNA methylation markers in peripheral blood mononuclear cells which are predictive of breast cancer across multiple cohorts.

引用

页数：13