Blood-borne miRNA profile-based diagnostic classifier for lung adenocarcinoma.
Blood-borne miRNA profile-based diagnostic classifier for lung adenocarcinoma.
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DOI：
10.1038/srep31389
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发表时间：
2016-08-10
影响因子：
4.6
通讯作者：
Takahashi T
中科院分区：
文献类型：
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作者：
Tai MC;Yanagisawa K;Nakatochi M;Hotta N;Hosono Y;Kawaguchi K;Naito M;Taniguchi H;Wakai K;Yokoi K;Takahashi T
越来越多的证据表明，各种类型的miRNA在肺癌中异常表达，并分泌到血液中。在这项研究中，我们基于对143名肺腺癌患者和49名健康受试者的训练队列的miRNA图谱的详细生物信息学分析，构建了一个血清诊断分类器，得到了一个20个基于miRNA的分类器。对肺腺癌患者(n = 110)、健康受试者(n = 52)和肺部良性疾病患者(n = 47)样本进行的独立队列验证显示，敏感性为89.1%，特异性为94.9%，曲线下面积为0.958。值得注意的是，90.8%的I期肺腺癌病例得到了正确诊断。有趣的是，该分类器还检测到了相对较高的鳞癌和大细胞肺癌病例(分别为70.4%和70.0%)，这似乎与癌症组织中器官部位依赖的miRNA表达一致。相比之下，我们从96例其他主要器官的癌症样本中观察到明显较低的比率(0-35%)，其中乳腺癌的比率最低。这些发现保证了未来的研究，以实现其作为肺癌诊断程序的一部分的临床应用，对于肺癌，早期发现和手术切除是目前最终治愈的唯一希望。
Accumulated evidence indicates that various types of miRNA are aberrantly expressed in lung cancer and secreted into the bloodstream. For this study, we constructed a serum diagnostic classifier based on detailed bioinformatics analysis of miRNA profiles from a training cohort of 143 lung adenocarcinoma patients and 49 healthy subjects, resulting in a 20 miRNA-based classifier. Validation performed with an independent cohort of samples from lung adenocarcinoma patients (n = 110), healthy subjects (n = 52), and benign pulmonary disease patients (n = 47) showed a sensitivity of 89.1% and specificity of 94.9%, with an area under the curve value of 0.958. Notably, 90.8% of Stage I lung adenocarcinoma cases were correctly diagnosed. Interestingly, this classifier also detected squamous and large cell lung carcinoma cases at relatively high rates (70.4% and 70.0%, respectively), which appears to be consistent with organ site-dependent miRNA expression in cancer tissues. In contrast, we observed significantly lower rates (0–35%) using samples from 96 cases of cancer in other major organs, with breast cancer the lowest. These findings warrant a future study to realize its clinical application as a part of diagnostic procedures for lung cancers, for which early detection and surgical removal is presently the only hope for eventual cure.