Decreased serum miR-181a is a potential new tool for breast cancer screening

Decreased serum miR-181a is a potential new tool for breast cancer screening
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DOI:
10.3892/ijmm.2012.1021
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发表时间:
2012-09-01
影响因子:
5.4
通讯作者:
Zhang, Qing-Yun
Zhang, Qing-Yun
中科院分区:
医学3区
文献类型:
--
作者:
Guo, Li-Juan;Zhang, Qing-Yun

文献摘要

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乳腺癌(BC)筛查对于早期发现很重要,但传统的肿瘤标志物缺乏预期的敏感性。微小RNA(MiRNA)的异常表达在肿瘤的形成和发展中起着重要作用。因此,血清miRNAs是潜在的BC生物标志物。MicroRNA-181a(miR-181a)在许多类型的人类癌症中被解除调控,是一个关键的致癌调节因子,但血清miR-181a与BC诊断的关系尚未被研究。本研究通过检测血清miR-181a水平,比较血清miR-181a作为BC肿瘤标志物与常规肿瘤标志物CA153、CEA的诊断价值。用实时荧光定量RT-PCR方法检测20例血浆标本中miR-181a和miR-16的含量。这些令人振奋的结果促使人们对227个额外的样本进行了分析。采用电化学发光法测定血清CA153和CEA水平。BC患者的miR-181a中位数水平显著低于健康对照组(P=0.001)。ROC分析显示miR-181a诊断乳腺癌的敏感性和特异性分别为70.7%和59.9%,而CA153和CEA的敏感性分别为10.53%和9.21%。作为一种肿瘤标志物,血清miR-181a对乳腺癌早期诊断的敏感性[55.28%(68/123)]高于CA153和CEA标志物(8.13%和7.32%)。MiR-181a水平与其他临床病理参数无明显相关性。这些结果表明,血清miR-181a可能是一种新的生物标志物,可用于原发性BC以及早期BC的诊断。血清miR-181a与其他标志物联合应用可提高筛查BC的敏感性。
Breast cancer (BC) screening is important for early detection, but conventional tumor markers lack the desired sensitivity. Aberrant microRNA (miRNA) expression plays an important role in tumor formation and development. Thus, serum miRNAs represent potential BC biomarkers. microRNA-181a (miR-181a) is deregulated in many types of human cancer and is a key oncogenic regulator, but the relationship between serum miR-181a and BC diagnosis has not been investigated. This study investigated serum miR-181a levels in BC patients and healthy controls and compared the diagnostic value of serum miR-181a as a BC tumor marker with the conventional tumor markers CA 153 and CEA. Serum miR-181a and miR-16 (as a control) were quantified by real-time quantitative RT-PCR in 20 plasma samples. The promising results prompted analysis of 227 additional samples. The levels of CA 153 and CEA were measured using electrochemiluminescence assays. Median miR-181a levels were significantly lower in patients with BC compared to healthy controls (P=0.001). ROC analysis demonstrated the sensitivity and specificity of miR-181a for BC diagnosis at 70.7 and 59.9%, respectively, whereas the sensitivities of CA 153 and CEA were 10.53 and 9.21%. As a tumor marker, serum miR-181a expressed a higher level of sensitivity [55.28% (68/123)] in the early stage of BC diagnosis (ductal carcinoma in situ, TNM I and II) than the CA 153 and CEA markers (8.13 and 7.32%, respectively). There were no significant associations between miR-181a levels and other clinicopathological parameters. These results suggest that serum miR-181a may represent a novel biomarker for primary BC as well as for early stage BC diagnosis. In combination with other markers, serum miR-181a may improve the sensitivity of BC screening.