循环 circRNA hsa_circ_0001785 可作为乳腺癌检测的诊断生物标志物。
Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for breast cancer detection.
机构信息
Department of Clinical Laboratory, The First People's Hospital of Shangqiu City, Shangqiu, Henan 476000, China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dali University, Dali, Yunnan 671000, China.
出版信息
Clin Chim Acta. 2018 Dec;487:363-368. doi: 10.1016/j.cca.2017.10.011. Epub 2017 Oct 16.
BACKGROUND
Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and characterized by covalently closed loop without 5' and 3' end. Recently, the diagnostic value of circRNAs has received more and more attention. However, the in-depth study about circRNAs diagnosis in breast cancer is still rarely reported. In present study, we try to investigate the circRNAs expression profiles in breast cancer peripheral blood and discover valuable diagnostic biomarkers.
METHODS
The expression profiles of circRNAs in plasma specimens were screened from five breast cancer and paired healthy volunteer s. The expression levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic value was performed using receiver operating characteristic (ROC) curve.
RESULTS
CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with 2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among these circRNAs, 3 candidate circRNAs were validated to be significantly dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover, in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3 (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients (0.283±0.043) was significantly lower than that of preoperative patients (0.109±0.037, P<0.01).
CONCLUSION
Our study reveals the aberrant circRNAs expression profiles in breast cancer peripheral blood, and identifies the potential diagnostic value of plasma hsa_circ_0001785, providing a stable biomarkers for the diagnosis and progress of breast cancer.
背景
环状 RNA（circRNAs）是一类非编码 RNA（ncRNAs），其特征是没有 5' 和 3' 末端的共价闭环。最近，circRNAs 的诊断价值受到了越来越多的关注。然而，关于乳腺癌中 circRNAs 诊断的深入研究仍很少报道。在本研究中，我们试图研究乳腺癌外周血中的 circRNAs 表达谱，并发现有价值的诊断生物标志物。
方法
从五例乳腺癌患者和五名配对的健康志愿者的血浆标本中筛选 circRNAs 的表达谱。通过 RT-PCR 检测选定候选 circRNAs 的表达水平。使用受试者工作特征（ROC）曲线进行诊断价值分析。
结果
circRNAs 微阵列分析显示，有 41 个 circRNAs 的表达发生了 2 倍变化，其中 19 个上调，22 个下调。在这些 circRNAs 中，通过 RT-PCR 验证了 3 个候选 circRNAs 显著失调，包括 hsa_circ_0001785、hsa_circ_0108942 和 hsa_circ_0068033。在更大的研究队列（n=20）中，ROC 曲线显示 hsa_circ_0001785 具有更好的诊断价值（AUC=0.771）。此外，在进一步的广泛研究队列（n=57）中，我们发现 hsa_circ_0001785 血浆具有更好的诊断准确性（AUC=0.784），优于 CEA（AUC=0.562）和 CA15-3（AUC=0.629）。此外，hsa_circ_0001785 血浆水平与组织学分级（P=0.013）、TNM 分期（P=0.008）和远处转移（P=0.016）密切相关。此外，术后患者（0.283±0.043）的 hsa_circ_0001785 血浆水平明显低于术前患者（0.109±0.037，P<0.01）。
结论
本研究揭示了乳腺癌外周血中异常的 circRNAs 表达谱，并确定了 hsa_circ_0001785 血浆的潜在诊断价值，为乳腺癌的诊断和进展提供了稳定的生物标志物。
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