miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma.
miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma.
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DOI：
10.1371/journal.pone.0101899
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Monzó M
中科院分区：
文献类型：
--
作者：
Tejero R;Navarro A;Campayo M;Viñolas N;Marrades RM;Cordeiro A;Ruíz-Martínez M;Santasusagna S;Molins L;Ramirez J;Monzó M
非小细胞肺癌（NSCLC）的几种治疗方法是组织学依赖性的，对组织学相关标志物的需求正在增加。微小RNA（miRNAs）是多种癌症中有前途的分子标记物，并且根据组织学亚型显示出表达差异。miRNA家族miR-200与上皮-间充质（EMT）/间充质-上皮转化（MET）的调节相关。EMT涉及深刻的表型变化，包括细胞-细胞粘附的丧失、细胞极性的丧失以及促进转移的迁移和侵袭性质的获得。miR-200家族在几种肿瘤预后中的双重作用与肿瘤细胞来源有关。然而，miR-200家族在早期NSCLC腺癌和鳞状细胞癌（SCC）中的预后作用和功能尚未得到很好的确定。使用TaqMan测定法测定来自切除的NSCLC患者的155个肿瘤中的miRNA表达。在三种NSCLC细胞系中进行了功能研究：H23、A-549和HCC-44。在整个队列中，高miR-200 c表达与较短的总生存期（OS）相关（p = 0.024）。 miR-200 c（p = 0.0004）和miR-141（p = 0.009）高表达与腺癌中较短的OS相关，但与SCC无关。 在多变量分析中，基于miR-141和miR-200 c表达的风险评分在整个队列（OR，2.787; p = 0.033）和腺癌患者（OR，10.649; p = 0.002）中成为OS的独立预后因素。 功能分析显示，miR-200 c与间充质-上皮转化（MET）相关，并影响细胞迁移和E-钙粘蛋白水平，而miR-141的过表达降低了KLF 6蛋白水平，并导致体外VEGFA分泌增加（H23，p = 0.04; A-549，p = 0.03; HCC-44，p = 0.02），并与患者肿瘤样本中较高的血管密度相关（p<0.001）。 miR-141和miR-200 c高表达通过MET和血管生成与NSCLC腺癌患者的OS较短相关。
Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established. miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44. High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p = 0.024). High miR-200c (p = 0.0004) and miR-141 (p = 0.009) expression correlated with shorter OS in adenocarcinoma – but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p = 0.033) and in adenocarcinoma patients (OR, 10.649; p = 0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p = 0.04; A-549, p = 0.03; HCC-44, p = 0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001). High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis.
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
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影响因子：
3.7
作者：
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Zhang W