Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.
Low levels of cell-free circulating miR-361-3p and miR-625* as blood-based markers for discriminating malignant from benign lung tumors.
复制标题
DOI：
10.1371/journal.pone.0038248
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schwarzenbach H
中科院分区：
文献类型：
--
作者：
Roth C;Stückrath I;Pantel K;Izbicki JR;Tachezy M;Schwarzenbach H
肺癌患者的高死亡率主要是由于肺癌被诊断为晚期。为了有效的癌症预防计划和早期诊断，需要更好的血液标记物。因此，基于血液的microRNA（miR）表达的微阵列分析进行术前血清中的21个非小细胞肺癌（NSCLC）患者和11个健康个体的微流体生物芯片含有1158个不同的miR。通过TaqMan MicroRNA检测，在97例NSCLC患者、20例良性肺病患者和30例健康个体的血清中进一步验证了30种最失调的miR中的两种。微阵列分析显示肺癌患者血清中miR-361- 3 p和miR-625* 表达显著下调。通过定量RT-PCR进一步评估显示，NSCLC中miR-361- 3 p和miR-625* 的水平低于良性疾病（p = 0.0001）和健康个体（分别为p= 0.0001，p =0.0005）。 此外，miR-625* 的水平在大细胞肺癌患者（LCLC，p = 0.014）和吸烟患者（p = 0.030）中分别显著低于腺癌患者和非吸烟患者。 与术前水平相比，在术后样本中观察到两种miR的水平升高（p = 0.0001）。 功能分析显示Smad 2和TGF β 1在肺细胞系A549中分别不受miR-361- 3 p和miR-625* 的失调。我们目前的初步研究表明，miR-361- 3 p和miR-625* 可能对NSCLC的发展具有保护作用，血清中这些miR的定量评估可能具有检测NSCLC的诊断潜力，特别是在吸烟者中。
The high mortality rate of lung cancer patients is mainly due to the late stage at which lung cancer is diagnosed. For effective cancer prevention programs and early diagnosis, better blood-based markers are needed. Hence, blood-based microarray profiling of microRNA (miR) expression was performed in preoperative serum of 21 non-small cell lung cancer (NSCLC) patients and 11 healthy individuals by microfluid biochips containing 1158 different miRs. Two out of the 30 most dysregulated miRs were further validated in serum of 97 NSCLC patients, 20 patients with benign lung diseases and 30 healthy individuals by TaqMan MicroRNA Assays. Microarray profiling showed that miR-361-3p and miR-625* were significantly down-regulated in serum of lung cancer patients. Their further evaluation by quantitative RT-PCR showed that the levels of miR-361-3p and miR-625* were lower in NSCLC than in benign disease (p = 0.0001) and healthy individuals (p = 0.0001, p = 0.0005, respectively). Moreover, the levels of miR-625* were significantly lower in patients with large cell lung cancer (LCLC, p = 0.014) and smoking patients (p = 0.030) than in patients with adenocarcinoma and non-smoking patients, respectively. A rise in the levels of both miRs was observed in the postoperative samples compared with the preoperative levels (p = 0.0001). Functional analyses showed that Smad2 and TGFß1 are not dysregulated by miR-361-3p and miR-625* in the lung cell line A549, respectively. Our present pilot study suggests that miR-361-3p and miR-625* might have a protective influence on the development of NSCLC, and the quantitative assessment of these miRs in blood serum might have diagnostic potential to detect NSCLC, in particular in smokers.
登录
查看更多内容
DOI：
10.1186/bcr2766
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Roth C;Rack B;Müller V;Janni W;Pantel K;Schwarzenbach H
通讯作者：
Schwarzenbach H
影响因子：
8
作者：
Liu, YJ;Xu, Y;Yu, Q
通讯作者：
Yu, Q
影响因子：
8
作者：
Muratovska, A;Zhou, CM;Eccles, MR
通讯作者：
Eccles, MR
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
影响因子：
3.6
作者：
Cohen, Ezra E. W.;Subramanian, Janakiraman;Vokes, Everett E.
通讯作者：
Vokes, Everett E.