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循环血浆微小RNA作为鉴定晚期非小细胞肺癌患者表皮生长因子受体(EGFR)突变状态及监测表皮生长因子受体-酪氨酸激酶抑制剂治疗的潜在标志物。

Circulating plasma microRNAs as potential markers to identify EGFR mutation status and to monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with advanced non-small cell lung cancer.

作者信息

Qu Lili, Li Liangliang, Zheng Xiaofei, Fu Hanjiang, Tang Chuanhao, Qin Haifeng, Li Xiaoyan, Wang Hong, Li Jianjie, Wang Weixia, Yang Shaoxing, Wang Lin, Zhao Guanhua, Lv Panpan, Lei Yangyang, Zhang Min, Gao Hongjun, Song Santai, Liu Xiaoqing

机构信息

Department of Lung Cancer, Affiliated Hospital of the Academy of Military Medical Science, Beijing, China.

Institute of Radiation Medicine, Academy of Military Medical Science, Beijing, China.

出版信息

Oncotarget. 2017 Jul 11;8(28):45807-45824. doi: 10.18632/oncotarget.17416.

Abstract

We aimed to identify a panel of circulating plasma microRNAs that can predict EGFR mutation status and monitor epidermal growth factor receptor-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer. Microarrays were performed for the preliminary screening of dysregulated microRNAs in 9 EGFR mutation-positive patients versus healthy controls. MiR-107 was upregulated and miR-195 was downregulated in the exon 19 deletion versus wild-type group. The areas under the receiver operating characteristic curves for miR-107, miR-195, and a panel of these 2 microRNAs were 0.72, 0.75, and 0.74, with sensitivities and specificities of 64.7% and 76.6%, 71.8% and 69.1%, and 71.7% and 78.9%, respectively. MiR-122 was significantly upregulated in the p.L858R versus wild-type group. An area under the receiver operative characteristic curve of 0.75 suggests that miR-122 might be a specific biomarker for patients with the p.L858R mutation. In addition, dynamic changes in these 3 microRNAs were also found to correlate with responses to epidermal growth factor receptor-tyrosine kinase inhibitor treatment, indicating that circulating plasma microRNAs may represent potential biomarkers for monitoring epidermal growth factor receptor-tyrosine kinase inhibitor treatment. This study demonstrates the prospective application of circulating plasma microRNAs as potential non-invasive, convenient biomarkers for patients with EGFR-sensitive mutations.

摘要

我们旨在鉴定一组循环血浆微小RNA,其可预测非小细胞肺癌患者的表皮生长因子受体(EGFR)突变状态并监测表皮生长因子受体-酪氨酸激酶抑制剂治疗。对9例EGFR突变阳性患者与健康对照进行微阵列分析,以初步筛选失调的微小RNA。在19外显子缺失组与野生型组中,miR-107上调而miR-195下调。miR-107、miR-195以及这两种微小RNA组成的一组的受试者工作特征曲线下面积分别为0.72、0.75和0.74,敏感性和特异性分别为64.7%和76.6%、71.8%和69.1%、71.7%和78.9%。在p.L858R组与野生型组中,miR-122显著上调。受试者工作特征曲线下面积为0.75表明,miR-122可能是p.L858R突变患者的特异性生物标志物。此外,还发现这3种微小RNA的动态变化与表皮生长因子受体-酪氨酸激酶抑制剂治疗反应相关,表明循环血浆微小RNA可能代表监测表皮生长因子受体-酪氨酸激酶抑制剂治疗的潜在生物标志物。本研究证明了循环血浆微小RNA作为EGFR敏感突变患者潜在的非侵入性、便捷生物标志物的前瞻性应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d97e/5542229/5f447e3211a8/oncotarget-08-45807-g001.jpg

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