发现潜在的血清和尿液中的 microRNA 作为用于乳腺癌和妇科癌症的微创生物标志物。
Discovery of potential serum and urine-based microRNA as minimally-invasive biomarkers for breast and gynecological cancer.
机构信息
Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany.
Faculty of Medicine, University of Freiburg, Freiburg, Germany.
出版信息
Cancer Biomark. 2020;27(2):225-242. doi: 10.3233/CBM-190575.
BACKGROUND
Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies.
OBJECTIVE
Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC).
METHODS
In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, 10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests.
RESULTS
Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis.
CONCLUSIONS
Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts.
背景
乳腺和妇科癌症中失调的 microRNAs（miRNAs）可能有助于提高女性恶性肿瘤的早期检测。
目的
鉴定血清和尿液中 miRNA 类型作为乳腺（BC）、子宫内膜（EC）和卵巢癌（OC）的微创生物标志物。
方法
在发现阶段，17 名 BC 患者、5 名 EC 患者和 5 名 OC 患者的血清和尿液样本与 10 名健康对照者（CTRL）进行了 Agilent 人类 miRNA 微阵列芯片分析。通过 RT-qPCR 在血清（31 名 BC 患者、13 名 EC 患者、15 名 OC 患者、32 名 CTRL）和尿液（25 名 BC 患者、10 名 EC 患者、10 名 OC 患者、30 名 CTRL）中进一步研究选定的 miRNA 类型，应用两样本 t 检验。
结果
由于表达水平的差异，一些 miRNA 生物标志物候选物具有诊断特征（血清：26；尿液：22）。其中，miR-518b、-4719 和 -6757-3p 在 BC 血清中被发现特异性失调。在尿液中，鉴定出 4 种具有未知功能作用的非实体特异性新型生物标志物候选物（miR-3973；-4426；-5089-5p 和 -6841）。RT-qPCR 鉴定出血清中的 miR-484/-23a（均 p ⩽ 0.001）可能作为 EC 和 OC 的潜在诊断标志物，而 miR-23a 也可能作为 BC 诊断的内参。
结论
有前途的 miRNAs 作为基于液体活检的工具，用于检测 BC、EC 和 OC，有资格在更大的队列中进行外部验证。
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