Department of Surgery, National University of Ireland, Galway, Ireland. Cos
Oncologist. 2010;15(7):673-82. doi: 10.1634/theoncologist.2010-0103. Epub 2010 Jun 24.
The potential of microRNAs (miRNAs) as novel tumor markers has been the focus of recent scrutiny because of their tissue specificity, stability, and association with clinicopathological parameters. Data have emerged documenting altered systemic miRNA expression across a spectrum of cancers; however, it remains uncertain as to whether circulating miRNAs are tumor specific. Our aim was to assess a panel of cancer-associated miRNAs in the circulation of patients with various malignancies, to determine whether these "oncomirs" were tumor specific, and thus to establish whether systemic miRNA analysis has utility in cancer diagnosis.
Whole blood samples were prospectively collected from preoperative cancer patients (breast, prostate, colon, and renal cancer and melanoma; n = 163) and healthy age- and sex-matched controls (n = 63). Total RNA was isolated, and a panel of seven miRNAs was quantified by real-time quantitative polymerase chain reaction in each sample.
Differential expression of the general oncomirs let 7a, miR-10b, and miR-155, was observed in the majority of cancer patients in a nonspecific manner. Significantly, elevated circulating miR-195 was found to be breast cancer specific and could differentiate breast cancer from other cancers and from controls with a sensitivity of 88% at a specificity of 91%. A combination of three circulating miRNAs, including miR-195, further enhanced the discriminative power of this test for breast cancer to 94%.
These findings suggest that individual cancers display specific systemic miRNA profiles, which could aid in discriminating among cancer types. This finding is of notable clinical consequence because it illustrates the potential of systemic miRNAs as sensitive, specific, noninvasive cancer biomarkers.
由于 miRNA(miRNA)具有组织特异性、稳定性和与临床病理参数的相关性,因此它们作为新型肿瘤标志物的潜力一直是最近研究的焦点。有数据表明,在一系列癌症中存在系统性 miRNA 表达改变;然而,循环 miRNA 是否具有肿瘤特异性尚不确定。我们的目的是评估一组癌症相关 miRNA 在各种恶性肿瘤患者循环中的表达,以确定这些“oncomirs”是否具有肿瘤特异性,从而确定系统性 miRNA 分析在癌症诊断中的应用价值。
前瞻性收集术前癌症患者(乳腺癌、前列腺癌、结肠癌、肾癌和黑色素瘤;n=163)和健康年龄及性别匹配对照者(n=63)的全血样本。从每个样本中提取总 RNA,并通过实时定量聚合酶链反应定量检测一组 7 个 miRNA。
在大多数癌症患者中,普遍的 oncomirs let 7a、miR-10b 和 miR-155 以非特异性方式表达差异。值得注意的是,发现循环 miR-195 的升高具有乳腺癌特异性,能够以 88%的敏感性和 91%的特异性将乳腺癌与其他癌症和对照组区分开来。三种循环 miRNA(包括 miR-195)的组合进一步增强了该检测对乳腺癌的区分能力,达到 94%。
这些发现表明,个体癌症显示出特定的系统性 miRNA 谱,这有助于区分癌症类型。这一发现具有显著的临床意义,因为它表明系统性 miRNAs 作为敏感、特异、非侵入性的癌症生物标志物具有潜力。