循环 miR-30b 和 miR-30c 可预测 EGFR 突变型非小细胞肺癌患者对厄洛替尼的反应。

Circulating miR-30b and miR-30c predict erlotinib response in EGFR-mutated non-small cell lung cancer patients.

机构信息

Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Lung Cancer. 2019 Sep;135:92-96. doi: 10.1016/j.lungcan.2019.07.005. Epub 2019 Jul 12.

DOI:10.1016/j.lungcan.2019.07.005

PMID:31447008

Abstract

OBJECTIVES

MiR-30b, miR-30c, miR-221 and miR-222 are known to induce gefitinib resistance in lung cancer cell lines with activation of mutations in the epidermal growth factor receptor (EGFR). However, the role of these four microRNAs in tyrosine kinase inhibitor (TKI)-resistance in non-small cell lung cancer (NSCLC) patients is unknown. Thus, the aim of this study was to investigate the predictive value of miR-30b, miR-30c, miR-221 and miR-222 in plasma from EGFR-mutated lung cancer patients receiving erlotinib.

MATERIALS AND METHODS

The cohort consisted of 29 EGFR-mutated lung cancer patients receiving erlotinib. Plasma levels of miR-30b, miR-30c, miR-221 and miR-222 were analyzed by qPCR from blood samples collected before treatment start. Plasma concentration of each microRNA was correlated to clinical outcome.

RESULTS

Plasma concentrations of miR-30b and miR-30c could be determined in all 29 patients. Low plasma concentrations of miR-30b and miR-30c showed significant correlation with superior progression-free survival (PFS) (miR-30b: HR = 0.303 [0.123-0.747], p < 0.05; miR-30c: HR = 0.264 [0.103-0.674], p < 0.05). Low plasma concentrations of miR-30c were also significantly correlated with superior overall survival (OS) (HR = 0.30 [0.094-0.954], p < 0.041).

CONCLUSION

High plasma concentrations of miR-30b and miR-30c predicted shorter PFS and OS. This implies that miR-30b and miR-30c could have clinical potential as biomarkers in EGFR-mutated lung cancer patients.

摘要

目的

miR-30b、miR-30c、miR-221 和 miR-222 已知可诱导 EGFR 突变的肺癌细胞系对吉非替尼产生耐药性。然而，这四种 microRNA 在非小细胞肺癌（NSCLC）患者对酪氨酸激酶抑制剂（TKI）耐药中的作用尚不清楚。因此，本研究旨在探讨 EGFR 突变型肺癌患者接受厄洛替尼治疗时血浆中 miR-30b、miR-30c、miR-221 和 miR-222 的预测价值。

材料和方法

该队列包括 29 名接受厄洛替尼治疗的 EGFR 突变型肺癌患者。在开始治疗前采集的血液样本中，通过 qPCR 分析了 miR-30b、miR-30c、miR-221 和 miR-222 的血浆水平。分析了每个 microRNA 的血浆浓度与临床结果的相关性。

结果

29 名患者的血浆 miR-30b 和 miR-30c 浓度均可确定。miR-30b 和 miR-30c 的低血浆浓度与无进展生存期（PFS）显著相关（miR-30b：HR=0.303[0.123-0.747]，p<0.05；miR-30c：HR=0.264[0.103-0.674]，p<0.05）。miR-30c 的低血浆浓度也与总生存期（OS）显著相关（HR=0.30[0.094-0.954]，p<0.041）。