MicroRNA expression profiles of whole blood in lung adenocarcinoma.

MicroRNA expression profiles of whole blood in lung adenocarcinoma.
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DOI:
10.1371/journal.pone.0046045
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Vachani A
Vachani A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Patnaik SK;Yendamuri S;Kannisto E;Kucharczuk JC;Singhal S;Vachani A

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多项研究显示肺癌与血浆中 microRNA 变化的关联表明循环 microRNA 生物标志物在疾病的非侵入性检测中具有实用性。我们检查了全血 microRNA 表达是否也反映了肺癌的存在,这可能是由于全身反应所致。使用锁核酸微阵列对 22 名肺腺癌患者和 23 名对照者的全血中 microRNA 的整体表达进行了定量,其中 10 名患者有放射学检测到的非癌性肺结节,另外 13 名患者由于吸烟史 > 20 包年而处于患肺癌的高风险。病例和对照在年龄方面存在显着差异,平均差异为 10.7 岁,但在性别、种族、吸烟史、血红蛋白、血小板计数或白细胞计数方面没有显着差异。在 1282 种量化的人类 microRNA 中,有 395 种 (31%) 被确定为在研究对象中表达,其中 96 种 (24%) 在病例和对照之间存在差异表达。使用线性核支持向量机 (SVM) 和最高评分对 (TSP) 方法对 microRNA 表达数据进行分类分析,并且对识别肺腺癌存在的分类器进行了内部交叉验证。在留一法交叉验证中,TSP 分类器的敏感性和特异性分别为 91% 和 100%。 SVM 的值均为 91%。在蒙特卡罗交叉验证中,TSP 的平均敏感性和特异性分别为 86% 和 97%,SVM 的平均敏感性和特异性分别为 88% 和 89%。 MicroRNA miR-190b、miR-630、miR-942 和 miR-1284 是分析过程中生成的分类器中最常见的成分。这些结果表明,全血 microRNA 表达谱可用于区分肺癌病例与临床相关对照。需要进一步的研究来验证这一观察结果,包括在非腺癌性肺癌中,并澄清年龄的混杂影响。
The association of lung cancer with changes in microRNAs in plasma shown in multiple studies suggests a utility for circulating microRNA biomarkers in non-invasive detection of the disease. We examined if presence of lung cancer is reflected in whole blood microRNA expression as well, possibly because of a systemic response. Locked nucleic acid microarrays were used to quantify the global expression of microRNAs in whole blood of 22 patients with lung adenocarcinoma and 23 controls, ten of whom had a radiographically detected non-cancerous lung nodule and the other 13 were at high risk for developing lung cancer because of a smoking history of >20 pack-years. Cases and controls differed significantly for age with a mean difference of 10.7 years, but not for gender, race, smoking history, blood hemoglobin, platelet count, or white blood cell count. Of 1282 quantified human microRNAs, 395 (31%) were identified as expressed in the study’s subjects, with 96 (24%) differentially expressed between cases and controls. Classification analyses of microRNA expression data were performed using linear kernel support vector machines (SVM) and top-scoring pairs (TSP) methods, and classifiers to identify presence of lung adenocarcinoma were internally cross-validated. In leave-one-out cross-validation, the TSP classifiers had sensitivity and specificity of 91% and 100%, respectively. The values with SVM were both 91%. In a Monte Carlo cross-validation, average sensitivity and specificity values were 86% and 97%, respectively, with TSP, and 88% and 89%, respectively, with SVM. MicroRNAs miR-190b, miR-630, miR-942, and miR-1284 were the most frequent constituents of the classifiers generated during the analyses. These results suggest that whole blood microRNA expression profiles can be used to distinguish lung cancer cases from clinically relevant controls. Further studies are needed to validate this observation, including in non-adenocarcinomatous lung cancers, and to clarify upon the confounding effect of age.
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