Circulating microRNAs predict the response to anti-PD-1 therapy in non-small cell lung cancer
Circulating microRNAs predict the response to anti-PD-1 therapy in non-small cell lung cancer
复制标题
循环 microRNA 预测非小细胞肺癌抗 PD-1 治疗的反应
DOI：
10.1016/j.ygeno.2019.11.019
复制
发表时间：
2020-03-01
期刊：
影响因子：
4.4
通讯作者：
Yang, Guanghai
中科院分区：
文献类型：
--
作者：
Fan, Jinshuo;Yin, Zhongyuan;Yang, Guanghai
迫切需要找到可靠的标记物来预测免疫治疗的疗效。我们试图研究血清microRNAs（miRNAs）和非小细胞肺癌（NSCLC）中检查点抑制剂反应之间的关联。进行血清miRNA谱的发现测定，证明27种血清miRNA（相对倍数> 2，p < .05），22种较高表达的和5种较低表达的miRNA，与27种非应答者相比，在19种应答者中差异表达。进一步验证证实miR-93、-138-5p、-200、-27a、-424、-34a、-28、-106b、-193a-3p和-181a在17个应答者相对于17个无应答者的独立队列中显著更高表达（p < .01）。纵向上，从治疗前到治疗后，应答者的miR-93、-138-5p、-200、-27 a、-424、-34 a、-28、-106 b、-193 a-3p和-181 a的血清表达水平增加（p < .01）。更重要的是，患者PFS的统计学显著改善与10-高表达的miRNA模式相关（中位PFS为6.25个月对3.21个月，p <0.001;风险比，HR，0.45; 95%CI，0.25-0.76）。进一步的OS改善也与应答者与非应答者中的10种高表达miRNA模式显著相关（中位OS为7.65个月与3.2个月，p <0.001，HR，0.39; 95%CI，0.15-0.68）。总之，这些结果表明，循环miRNA的改变与抗PD 1药物治疗的NSCLC患者的应答和结局相关。
Finding reliable markers for predicting the efficacy of immunotherapy is urgently needed. We sought to investigate the association between serum microRNAs (miRNAs) and checkpoint inhibitor response in non-small cell lung cancer (NSCLC). Discovery assay with sera miRNA profiling was performed, demonstrating 27 sera miRNAs (relative fold > 2, p < .05), 22 higher expressed and 5 lower expressed miRNAs, were differentially expressed in 19 responders compared to those in 27 non-responders. Further validation validated miR-93, -138-5p, - 200, - 27a, - 424, - 34a, - 28, -106b, -193a-3p, and -181a were significantly higher expressed (p < .01) in an independent cohort of 17 responders vs. 17 non-responders. Longitudinally, responders had increased sera expression levels of miR-93, -138-5p, - 200, - 27a, - 424, - 34a, - 28, -106b, -193a-3p, and -181a from pre-treatment to post-treatment (p < .01). More importantly, statistically significant improvement in PFS of patients was associated with the 10-high expressed miRNA pattern (median PFS of 6.25 versus 3.21 months, p < .001; hazard ratio, HR, 0.45; 95% CI, 0.25-0.76). Further OS improvement was also significantly associated with the 10-high expressed miRNA pattern in responders versus non-responders (median OS of 7.65 versus 3.2 months, p < .001, HR, 0.39; 95% CI, 0.15-0.68). In conclusion, these results demonstrated that alterations in circulating miRNAs are associated with the response and outcome in NSCLC patients treated with anti-PD1 drugs.