Systemic miRNA-195 Differentiates Breast Cancer from Other Malignancies and Is a Potential Biomarker for Detecting Noninvasive and Early Stage Disease
Systemic miRNA-195 Differentiates Breast Cancer from Other Malignancies and Is a Potential Biomarker for Detecting Noninvasive and Early Stage Disease
复制标题
DOI：
10.1634/theoncologist.2010-0103
复制
发表时间：
2010-07-01
期刊：
影响因子：
5.8
通讯作者：
Kerin, Michael J.
中科院分区：
文献类型：
--
作者：
Heneghan, Helen M.;Miller, Nicola;Kerin, Michael J.
目的. microRNA（miRNAs）作为新型肿瘤标志物的潜力由于其组织特异性、稳定性以及与临床病理参数的相关性而成为最近研究的焦点。已经出现的数据记录了在一系列癌症中改变的系统性miRNA表达;然而，关于循环miRNA是否具有肿瘤特异性仍然不确定。我们的目的是评估在患有各种恶性肿瘤的患者的循环中的一组癌症相关的miRNA，以确定这些“oncomirs”是否是肿瘤特异性的，从而确定系统性miRNA分析是否在癌症诊断中具有实用性。前瞻性采集术前癌症患者（乳腺癌、前列腺癌、结肠癌、肾癌和黑色素瘤; n = 163）和年龄和性别匹配的健康对照组（n = 63）的全血样本。提取总RNA，通过实时定量聚合酶链反应对每个样本中的7种miRNAs进行定量。在大多数癌症患者中以非特异性方式观察到一般on-comirs let 7a、miR-10 b和miR-155的差异表达。值得注意的是，发现循环miR-195升高具有乳腺癌特异性，并且可以将乳腺癌与其他癌症和对照区分开来，灵敏度为88%，特异性为91%。包括miR-195在内的三种循环miRNA的组合进一步提高了该检测对乳腺癌的区分能力至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，因为它说明了系统性miRNA作为敏感、特异、非侵入性癌症生物标志物的潜力。肿瘤学家2010;15：673-682
Purpose. 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.Patients and Methods. 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.Results. Differential expression of the general on-comirs 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%.Conclusion. 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. The Oncologist 2010;15:673-682