Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection. Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers. Overall design: Analyze 5-hydroxymethyl cytosine (5hmC) genome-wide distribution in plasma cell-free DNA from bladder, breast, colorectal, kidney, lung, and prostate cancer patients in comparison to non-cancer controls

本研究采用高灵敏度的nano-5hmC-Seal方法，对384例膀胱癌、乳腺癌、结直肠癌、肾癌、肺癌或前列腺癌患者，以及221例对照个体的血浆游离DNA（cell-free DNA, cfDNA）中的5-羟甲基胞嘧啶（5-hydroxymethylcytosine, 5hmC）开展全基因组分布图谱分析。本研究借助机器学习技术，构建了可用于癌症检测及癌种溯源的高灵敏度血浆cfDNA 5hmC特征标志物。同时，本研究鉴定出上述六种癌症中存在DNA羟甲基化异常的基因与信号通路。整体实验设计：对比分析膀胱癌、乳腺癌、结直肠癌、肾癌、肺癌、前列腺癌患者与非癌症对照个体的血浆游离DNA中5-羟甲基胞嘧啶的全基因组分布情况。