Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.

Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers.
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DOI:
10.1002/ijc.25289
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发表时间:
2010-12-15
影响因子:
6.4
通讯作者:
Jiang, Feng
Jiang, Feng
中科院分区:
医学1区
文献类型:
--
作者:
Yu, Lei;Todd, Nevins W.;Xing, Lingxiao;Xie, Ying;Zhang, Howard;Liu, Zhenqiu;Fang, HongBin;Zhang, Jian;Katz, Ruth L.;Jiang, Feng

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腺癌是最常见的肺癌类型,是世界上癌症死亡的主要原因。早期发现是提高肺腺癌患者生存率的关键。我们之前已经证明 microRNA 稳定存在于痰中,可应用于肺癌的诊断。本研究的目的是开发一组 microRNA,可用作高度敏感和特异性的痰标志物,用于早期检测肺腺癌。这项研究分为三个阶段:(1) 使用 microRNA 分析对 20 名肺腺癌患者的配对正常肺组织和肿瘤肺组织进行标记物发现; (2) 通过实时 RT-qPCR 对由 36 名癌症患者和 36 名健康个体组成的病例对照队列的痰液进行标记物优化; (3) 对 64 名肺癌患者和 58 名无癌症受试者的独立组进行验证。从手术组织中,鉴定出 7 种表达显着改变的 microRNA,其中在所有 20 个肿瘤中“四种”过表达,“三种”表达不足。在病例对照队列的痰样本中,选择了 7 种 microRNA 中的 4 种(miR-21、miR-486、miR-375 和 miR-200b),它们组合起来产生了区分肺腺癌患者和正常受试者的最佳预测,敏感性为 80.6%,特异性为 91.7%。在独立人群中对标记物组的验证证实了其敏感性和特异性,与任何单独的标记物组相比,其具有显着的改进。痰标记物证明了转化为实验室环境以改善肺腺癌早期检测的潜力。
Adenocarcinoma is the most common type of lung cancer, the leading cause of cancer deaths in the world. Early detection is the key to improve the survival of lung adenocarcinoma patients. We have previously shown that microRNAs were stably present in sputum and could be applied to diagnosis of lung cancer. The aim of this study was to develop a panel of microRNAs that can be used as highly sensitive and specific sputum markers for early detection of lung adenocarcinoma. This study contained three phases: (1) marker discovery using microRNA profiling on paired normal and tumor lung tissues from 20 patients with lung adenocarcinoma; (2) marker optimization by real-time RT-qPCR on sputum of a case-control cohort consisting of 36 cancer patients and 36 health individuals; and (3) validation on an independent set of 64 lung cancer patients and 58 cancer-free subjects. From the surgical tissues, seven microRNAs with significantly altered expression were identified, of which “four” were overexpressed and “three” were underexpressed in all 20 tumors. On the sputum samples of the case-control cohort, four (miR-21, miR-486, miR-375, and miR-200b) of the seven microRNAs were selected, which in combination produced the best prediction in distinguishing lung adenocarcinoma patients from normal subjects with 80.6% sensitivity and 91.7% specificity. Validation of the marker panel in the independent populations confirmed the sensitivity and specificity that provided a significant improvement over any single one alone. The sputum markers demonstrated the potential of translation to laboratory settings for improving the early detection of lung adenocarcinoma.
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