5-Hydroxymethylcytosine signatures in circulating cell-free DNA as potential diagnostic markers for breast cancer

Breast cancer is one of the most prevalent cancers among women, and early diagnosis is crucial in reducing the mortality rate. This study aims to identify novel, reliable, and specific biomarkers for breast cancer diagnosis using 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA). We utilized the sensitive 5hmC seal method to map 5hmC profiles in cfDNA samples from 203 breast cancer patients and 60 healthy individuals. Machine learning models were applied to identify 5hmC marker signatures with high sensitivity and specificity. A global loss of 5hmC was observed in the blood samples from cancer patients compared to the control group. Several specific 5hmC marker signatures were identified, providing a basis for distinguishing between tumor and healthy individuals. Our study offers a comprehensive understanding of genome-wide 5hmC in cfDNA from breast cancer patients, and identifies valuable epigenetic biomarkers for the minimally invasive diagnosis of breast cancer.

乳腺癌是女性群体中最常见的恶性肿瘤之一，早期诊断对于降低死亡率至关重要。本研究旨在利用循环游离DNA（circulating cell-free DNA, cfDNA）中的5-羟甲基胞嘧啶（5-Hydroxymethylcytosine, 5hmC）特征，筛选可用于乳腺癌诊断的新型、可靠且特异性的生物标志物。本研究采用灵敏度优异的5hmC封闭标记法，对203名乳腺癌患者与60名健康对照者的cfDNA样本进行5hmC全谱分析。通过机器学习模型筛选出具有高灵敏度与特异性的5hmC特征标志物。相较于健康对照组，乳腺癌患者的血液样本中呈现出全基因组范围内的5hmC丢失现象。本研究筛选出多个特异性5hmC特征标志物，可作为区分肿瘤患者与健康个体的依据。本研究全面解析了乳腺癌患者cfDNA的全基因组5hmC分布特征，并筛选出可用于乳腺癌微创诊断的极具价值的表观遗传生物标志物。