从卵巢癌患者血清中检测新型 miRNA 作为上皮性卵巢癌的生物标志物。
Detection of microRNA as novel biomarkers of epithelial ovarian cancer from the serum of ovarian cancer patients.
机构信息
Department of Obstetrics and Gynecology, Korea University Medical Center, Seoul, Korea.
出版信息
Int J Gynecol Cancer. 2013 May;23(4):673-9. doi: 10.1097/IGC.0b013e31828c166d.
OBJECTIVE
MicroRNA (miRNA) is an abundant class of small noncoding RNAs that act as gene regulators. Recent studies have suggested that miRNA deregulation is associated with the initiation and progression of human cancer. However, information about cancer-related miRNA is mostly limited to tissue miRNA. The aim of this study was to find specific profiles of serum-derived miRNAs of ovarian cancer based on a comparative study using a miRNA microarray of serum, tissue, and ascites.
METHODS
From 2 ovarian cancer patients and a healthy control, total RNA was isolated from their serum, tissue, and ascites, respectively, and analyzed by a microarray. Under the comparative study of each miRNA microarray, we sorted out several miRNAs showing a consistent regulation tendency throughout all 3 specimens and the greatest range of alteration in serum as potential biomarkers. The availability of biomarkers was confirmed by qRT-PCR of 18 patients and 12 controls.
RESULTS
Out of 2222 kinds of total miRNAs that were identified in the microarray analysis, 95 miRNAs were down-regulated and 88 miRNAs were up-regulated, in the serum, tissue, and ascites of cancer patients. Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR.
CONCLUSIONS
Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer. Also, serum miRNAs is a promising and useful tool for discriminating between controls and patients with serous ovarian cancer.
目的
miRNA（miRNA）是一类丰富的小非编码 RNA，作为基因调节剂发挥作用。最近的研究表明，miRNA 失调与人类癌症的发生和发展有关。然而，关于癌症相关 miRNA 的信息主要局限于组织 miRNA。本研究旨在通过对血清、组织和腹水 miRNA 微阵列的比较研究，找到卵巢癌血清衍生 miRNA 的特定谱。
方法
从 2 名卵巢癌患者和 1 名健康对照者中分别分离其血清、组织和腹水的总 RNA，并通过微阵列进行分析。在每个 miRNA 微阵列的比较研究中，我们整理出几种在所有 3 种标本中表现出一致调节趋势且在血清中变化最大的 miRNA，作为潜在的生物标志物。通过对 18 名患者和 12 名对照者进行 qRT-PCR 验证了生物标志物的可用性。
结果
在微阵列分析中鉴定出的 2222 种总 miRNA 中，有 95 种 miRNA 下调，88 种 miRNA 上调，在癌症患者的血清、组织和腹水中。在所有标本中表现出一致调节趋势且在血清中差异大于 2 倍的 miRNA 中，miR-132、miR-26a、let-7b、miR-145 和 miR-143 被确定为卵巢癌患者血清中最显著下调的 5 种 miRNA。在 qRT-PCR 中，5 个选定 miRNA 中的 4 个（miR-132、miR-26a、let-7b 和 miR-145）在卵巢癌患者的血清中表达明显下调。
结论
血清 miR-132、miR-26a、let-7b 和 miR-145 可被视为浆液性卵巢癌新型生物标志物的潜在候选物。此外，血清 miRNAs 是区分浆液性卵巢癌患者和对照者的一种很有前途和有用的工具。
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