Department of Surgery, The University of Hong Kong, Hong Kong, China.
PLoS One. 2013;8(1):e53141. doi: 10.1371/journal.pone.0053141. Epub 2013 Jan 3.
We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection.
METHODOLOGY/PRINCIPAL FINDINGS: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%.
These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.
我们之前的研究表明，血浆中的 microRNAs（miRNAs）可能是结直肠癌检测的潜在生物标志物。在此，我们旨在开发用于乳腺癌检测的特定血液 miRNA 检测方法。
方法/主要发现：对乳腺癌患者的肿瘤、相邻非肿瘤组织以及相应的血浆，以及匹配的健康对照者的血浆进行了基于 TaqMan 的 miRNA 分析。在乳腺癌患者的训练组中验证了所有鉴定出的潜在标志物。在一个包含 170 例乳腺癌患者、100 例对照者和 95 例其他类型癌症的病例对照队列中验证了选定的标志物，然后在一个包含 70 例乳腺癌患者和 50 例健康对照者的独立队列中进行了盲法验证。分析结果显示，8 种 miRNA 在乳腺癌患者的血浆和肿瘤组织中均呈上调，而 1 种 miRNA 呈下调。在训练组中，这 8 个上调 miRNA 中只有 3 个在术前显著升高（p<0.0001），且在术后降低。验证队列的结果表明，miR-145 和 miR-451 的组合是区分乳腺癌与健康对照者和所有其他类型癌症的最佳生物标志物（p<0.0001）。在盲法验证中，这些血浆标志物的受试者工作特征（ROC）曲线下面积为 0.931。阳性预测值为 88%，阴性预测值为 92%。这些 miRNA 在血浆中的异常水平不仅在晚期肿瘤中，而且在肿瘤的早期阶段也能被检测到。导管原位癌（DCIS）病例的阳性预测值为 96%。
这些结果表明，这些循环 miRNA 可能是乳腺癌筛查的潜在特异性生物标志物。
