Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma
Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma
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DOI：
10.3892/mmr.2013.1517
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发表时间：
2013-08-01
影响因子：
3.4
通讯作者：
Betsuyaku, Tomoko
中科院分区：
文献类型：
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作者：
Hamamoto, Junko;Soejima, Kenzo;Betsuyaku, Tomoko
新药治疗非小细胞肺癌（NSCLC）的最新进展需要在诊断时进行准确的组织学亚型，以避免不良反应的较高风险并获得最大的治疗反应。然而，观察者间的变异性、肿瘤异质性和分化程度可能会影响 NSCLC 病理诊断的决定。因此，本研究的目的是鉴定特定的microRNA（miRNA）作为具有高敏感性和特异性的标准化生物标志物，以区分鳞状细胞癌（SCC）和腺癌（AC）。除了邻近的正常组织外，还使用 86 个切除的 NSCLC 样本进行基于定量聚合酶链反应 (qPCR) 的 miRNA 阵列分析，以鉴定 SCC 和 AC 之间差异表达的 microRNA。结果通过使用相同测试样本和 88 个额外验证样本的独立 qRT-PCR 测定得到证实，并据此我们评估了已识别的 miRNA 作为区分 SCC 和 AC 的生物标志物的有用性。鉴定出三种 miRNA（hsa-miR-196b、hsa-miR-205 和 hsa-miR-375）。结合这三种 miRNA 的判别分析似乎可以在测试和验证样本中准确地区分 SCC 和 AC，其灵敏度和特异性分别为 76% 和 80%、85% 和 83%。 hsa-miR-196b、hsa-miR-205 和 hsa-miR-375 被确定为能够区分肺 SCC 和肺 AC 的生物标志物。这些新发现的miRNA可能被证明是对于NSCLC组织学亚型分类非常有价值的分子标记，并且可能有助于NSCLC每个亚型的发病机制。
Recent advances in the treatment of non-small cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis to avoid the higher risk of an adverse response and to obtain the maximum therapeutic response. However, interobserver variability, tumor hetero-geneity and the degree of differentiation may affect the decision concerning a pathological diagnosis of NSCLC. Therefore, the aim of this study was to identify specific microRNAs (miRNAs) as standardized biomarkers with high sensitivity and specificity in order to distinguish between squamous cell carcinoma (SCC) and adenocarcinoma (AC). Quantitative polymerase chain reaction (qPCR)-based miRNA array analysis was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples in addition to adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and 88 additional validation samples, and from this we evaluated the usefulness of the identified miRNAs as biomarkers to distinguish between SCC and AC. Three miRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining the three miRNAs appeared to distinguish SCC from AC accurately in the test and validation samples, demonstrating a sensitivity and specificity of 76 and 80%, and 85 and 83%, respectively. hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified miRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histological subtypes and may contribute to the pathogenesis of each subtype of NSCLC.