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

Tiantian Wang, Peilong Li, Qiuchen Qi, Shujun Zhang, Yan Xie, Jing Wang, Shibiao Liu, Suhong Ma, Shijun Li, Tingting Gong, Huiting Xu, Mengqiu Xiong, Guanghua Li, Chongge You, Zhaofan Luo, Juan Li (), Lutao Du () and Chuanxin Wang ()
Additional contact information
Tiantian Wang: The Second Hospital of Shandong University
Peilong Li: The Second Hospital of Shandong University
Qiuchen Qi: The Second Hospital of Shandong University
Shujun Zhang: The Second Hospital of Shandong University
Yan Xie: The Second Hospital of Shandong University
Jing Wang: The Second Hospital of Shandong University
Shibiao Liu: The Second Hospital of Shandong University
Suhong Ma: The Second Hospital of Shandong University
Shijun Li: The First Hospital of Dalian Medical University
Tingting Gong: The First Affiliated Hospital of Anhui Medical University
Huiting Xu: Affiliated Tumor Hospital of Nantong University, 226361, Jiangsu, China; Medical School of Nantong University
Mengqiu Xiong: Nanjing Medical University
Guanghua Li: Guangdong Provincial People’s Hospital/Guangdong Academy of Medical Sciences
Chongge You: Lanzhou University Second Hospital, the Second Clinical Medical College of Lanzhou University
Zhaofan Luo: The Seventh Affiliated Hospital of Sun Yat-Sen University
Juan Li: The Second Hospital of Shandong University
Lutao Du: The Second Hospital of Shandong University
Chuanxin Wang: The Second Hospital of Shandong University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-40389-5

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