Department of Research and Development, MiRXES Lab, Singapore, Singapore.
Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
Br J Cancer. 2022 Feb;126(3):472-481. doi: 10.1038/s41416-021-01593-6. Epub 2022 Jan 10.
Mammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening.
This study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379). Quantitative PCR profiling of 324 miRNAs was performed on serum samples from breast cancer (all stages) and healthy subjects to identify miRNA biomarkers. Two-fold cross-validation was used for building and optimising breast cancer-associated miRNA panels. An optimal panel was validated in cohorts with Caucasian and Asian samples. Diagnostic ability was evaluated using area under the curve (AUC) analysis.
The study identified and validated 30 miRNAs dysregulated in breast cancer. An optimised eight-miRNA panel showed consistent performance in all cohorts and was successfully validated with AUC, accuracy, sensitivity, and specificity of 0.915, 82.3%, 72.2% and 91.5%, respectively. The prediction model detected breast cancer in both Caucasian and Asian populations with AUCs ranging from 0.880 to 0.973, including pre-malignant lesions (stage 0; AUC of 0.831) and early-stage (stages I-II) cancers (AUC of 0.916).
Our panel can potentially be used for breast cancer screening, in conjunction with mammography.
乳腺 X 线摄影术被广泛用于乳腺癌筛查，但存在较高的假阳性率。在此，我们进行了迄今为止最大规模的、涉及不同种族群体的综合多中心研究，旨在寻找用于乳腺癌筛查的循环 miRNA。
本研究包括发现阶段（n=289）和两个验证阶段（n=374 和 n=379）。对乳腺癌（所有阶段）和健康受试者的血清样本进行了 324 个 miRNA 的定量 PCR 分析，以鉴定 miRNA 生物标志物。使用两倍交叉验证来构建和优化与乳腺癌相关的 miRNA 面板。在具有白人和亚洲人群样本的队列中验证最优面板。使用曲线下面积（AUC）分析评估诊断能力。
该研究鉴定并验证了 30 个在乳腺癌中失调的 miRNA。一个优化的 8-miRNA 面板在所有队列中表现一致，其 AUC、准确性、敏感性和特异性分别为 0.915、82.3%、72.2%和 91.5%，成功得到验证。该预测模型在白人和亚洲人群中均能检测乳腺癌，AUC 范围为 0.880 至 0.973，包括癌前病变（0 期；AUC 为 0.831）和早期（I-II 期）癌症（AUC 为 0.916）。
我们的面板可能与乳腺 X 线摄影术联合用于乳腺癌筛查。
