Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, 325027, China.
Mol Cancer. 2021 Feb 19;20(1):36. doi: 10.1186/s12943-021-01330-w.
Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.
早期发现对于改善乳腺癌（BC）患者的预后和生存至关重要。乳腺 X 线摄影和超声检查采用乳腺影像报告和数据系统（BI-RADS）分类，广泛用于 BC 的早期检测，但假阳性率高，导致不必要的活检，尤其是在 BI-RADS 4 类患者中。携带 DNA 甲基化信息的无细胞血浆 DNA（cfDNA）已成为癌症检测的一种非侵入性方法。在这里，我们提出了一项前瞻性多中心研究，该研究使用全基因组亚硫酸氢盐测序数据，针对 203 名疑似恶性乳腺病变的女性患者的 cfDNA 甲基化标志物的临床应用进行了研究。cfDNA 富含低甲基化的基因组区域。设计了一种实用的计算框架来挖掘最佳的 cfDNA 丰富的 DNA 甲基化标志物，这显著提高了 BI-RADS 4 类患者的早期诊断（AUC 从 0.78-0.79 提高到 0.93-0.94）。作为概念验证研究，我们以单碱基分辨率进行了首次基于血液的全基因组 DNA 甲基化检测早期乳腺癌良性肿瘤的研究，这表明将液体活检与传统诊断成像相结合可以通过降低假阳性率和避免不必要的伤害来改善当前的临床实践。
