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微小RNA let-7a表达对肺癌脑转移患者放疗疗效及预后的预测价值:一项病例对照研究

Predictive value of microRNA let-7a expression for efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis: A case-control study.

作者信息

Liu Ji-Kuan, Liu Hong-Feng, Ding Yong, Gao Guo-Dong

机构信息

Department of Thoracic Surgery, Jining No.1 People's Hospital, Jining.

Department of Surgery, Weishan People's Hospital, Weishan, Shandong Province, P.R. China.

出版信息

Medicine (Baltimore). 2018 Nov;97(44):e12847. doi: 10.1097/MD.0000000000012847.

Abstract

BACKGROUND

As a well-known cancer with high mortality, lung cancer has been implied to be closely associated with brain metastasis. Despite notable advances, effective treatment methods are still in urgent need. This study aims to investigate the value of serum microRNA-let-7a (miR-let-7a) expression in predicting efficacy and prognosis of radiotherapy in patients with lung cancer brain metastasis.

METHODS

To begin with, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for better understand of the correlation between miR-let-7a and lung cancer. Afterwards, the relationship between serum miR-let-7a expression and radiotherapy efficacy was analyzed by receiver operating characteristic curve analysis. Following successful transfection, RT-qPCR and Western blot assay were utilized for evaluating the involvement of miR-let-7a in regulation of DICER1 expression in lung cancer cell line. Then, whether miR-let-7a was implicated in proliferation and cell cycle distribution of lung cancer cells were confirmed by cell counting kit-8 assay and flow cytometry respectively.

RESULTS

Initially, it was revealed that serum miR-let-7a expression was decreased in lung cancer. Later, we found that decreased miR-let-7a displayed an unfavorable role in radiotherapy efficacy and overall survival rate of patients with lung cancer brain metastasis. After the successful transfection, the inverse relationship between miR-let-7a and DICER1 expression was uncovered. Meanwhile, biological behaviors of lung cancer cells were presented to be limited after transfection of overexpressed miR-let-7a.

CONCLUSION

Our findings demonstrated that the lower expression of miR-let-7a in patients with lung cancer brain metastasis was closely related to unfavorable efficacy and prognosis of radiotherapy, and it may be an important predictive biomarker by regulation of DICER1.

摘要

背景

肺癌作为一种死亡率高的知名癌症,一直被认为与脑转移密切相关。尽管取得了显著进展,但仍迫切需要有效的治疗方法。本研究旨在探讨血清微小RNA-let-7a(miR-let-7a)表达在预测肺癌脑转移患者放疗疗效和预后中的价值。

方法

首先,进行逆转录定量聚合酶链反应(RT-qPCR)以更好地了解miR-let-7a与肺癌之间的相关性。之后,通过受试者工作特征曲线分析血清miR-let-7a表达与放疗疗效之间的关系。成功转染后,利用RT-qPCR和蛋白质免疫印迹法评估miR-let-7a在肺癌细胞系中对DICER1表达的调控作用。然后,分别通过细胞计数试剂盒-8法和流式细胞术确认miR-let-7a是否参与肺癌细胞的增殖和细胞周期分布。

结果

最初发现肺癌患者血清miR-let-7a表达降低。后来发现,miR-let-7a降低对肺癌脑转移患者的放疗疗效和总生存率具有不利影响。成功转染后,发现miR-let-7a与DICER1表达呈负相关。同时,过表达miR-let-7a转染后肺癌细胞的生物学行为受到限制。

结论

我们的研究结果表明,肺癌脑转移患者中miR-let-7a的低表达与放疗疗效不佳和预后密切相关,它可能通过调控DICER1成为一个重要的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c6c/6221706/a1f1fc594f54/medi-97-e12847-g002.jpg

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