High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer

High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer
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DOI:
10.1007/s12032-011-9923-y
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发表时间:
2012-06-01
期刊:
影响因子:
3.4
通讯作者:
Zhang, Yong-Kui
Zhang, Yong-Kui
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Xiao-Guang;Zhu, Wang-Yu;Zhang, Yong-Kui

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血清microrna已被确定为潜在的癌症生物标志物。然而,microrna表达促进NSCLC发展和诊断的详细机制尚不清楚。本研究旨在鉴定诊断或预测NSCLC患者预后的特异性miRNA及其在组织和血清中表达的相关性。采用miRNA芯片分析了6例非小细胞肺癌患者的癌组织和非癌组织。其中,通过定量逆转录聚合酶链反应(qRT-PCR)检测了70例NSCLC配对样本(癌症、正常组织和血清)和44例正常志愿者血清样本中的3种mirna (miR-21、miR-141和miR-200c)。与芯片结果一致,miR-21、miR-141和miR-200c在NSCLC中的表达水平高于正常组织。癌症患者血清中miR-21水平较正常人升高,而miR-141和miR-200c在癌症患者血清中的表达水平较低。血清miR-21过表达与NSCLC的淋巴结转移和晚期临床分期密切相关。最后,log-rank和Cox回归检验表明,肿瘤miR 21和miR-200c或血清miR-21的高表达与NSCLC患者的低生存率相关。我们的研究结果表明,肿瘤miR-21、miR-141、miR-200c和血清miR-21可能是诊断非小细胞肺癌的潜在新型生物标志物。此外,本研究首次发现肿瘤miR-200c在预测NSCLC患者预后中的重要作用。
Serum microRNAs have been identified as potential cancer biomarkers. However, the detailed mechanism by which expression of microRNAs contributes to the development and diagnosis of NSCLC remains unknown. This study was to identify specific miRNAs for diagnosing or predicting the prognosis of NSCLC patients and their correlation between miRNA expression in tissues and serums. Six matched cancer and noncancerous tissues from NSCLC patients were analyzed by miRNA microarray. Among these, three miRNAs (miR-21, miR-141, and miR-200c) were examined in 70 NSCLC paired samples (cancer, normal tissue, and serum) and 44 serum samples of normal volunteers by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Consisting with the microarray results, the expression levels of miR-21, miR-141, and miR-200c in NSCLC were higher than those in normal tissues. While the level of serum miR-21 was increased in cancer patients as compared with that in normal counterpart, expression of miR-141 and miR-200c showed lower levels in serums from cancer patients. Overexpression of serum miR-21 was strongly associated with lymph node metastasis and advanced clinical stage of NSCLC. Finally, log-rank and Cox regression tests demonstrated that high expressions of tumor miR 21 and miR-200c or serum miR-21 were associated with a poor survival in NSCLC patients. Our results suggest that tumor miR-21, miR-141, miR-200c, and serum miR-21 may be potential novel biomarkers for the diagnosis of NSCLC. In addition, this study, for the first time, identifies a significant role of the tumor miR-200c played in predicting prognosis in patients with NSCLC.