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Annals of surgery 血浆miR-181a-5p下调可预测胰腺导管腺癌FOLFIRINOX后的反应和生存改善。

影响因子：13.787 DOI：10.1097/SLA.0000000000003084

作者： Meijer LL,Garajová I,Caparello C,Le Large TYS,Frampton AE,Vasile E,Funel N,Kazemier G,Giovannetti E 发表时间：2020-07-10 10:03:24

from：《ANNALS OF SURGERY》

keywords： Meijer LLGarajová ICaparello CLe Large TYSFrampton AEVasile EFunel NKazemier GGiovannetti E

关键词：

Abstract

OBJECTIVE:The aim of the study was to identify plasma microRNA (miRNA) biomarkers for stratifying and monitoring patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX, and to investigate their functional roles. SUMMARY BACKGROUND DATA:FOLFIRINOX has become a standard therapy for patients with advanced PDAC and can be used to potentially downstage disease. However, only a subset of patients respond, and biomarkers to guide decision-making are urgently needed. METHODS:We used microarray-based profiling to discover deregulated miRNAs in pre- and postchemotherapy plasma samples from patients based on their progression-free survival (PFS) after FOLFIRINOX. Nine candidate plasma miRNAs were validated in an independent cohort (n = 43). The most discriminative plasma miRNA was correlated with clinicopathological factors and survival, and also investigated in an additional cohort treated with gemcitabine plus nab-paclitaxel. Expression patterns were further evaluated in matched tumor tissues. In vitro studies explored its function, key downstream gene-targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. RESULTS:Plasma miR-181a-5p was significantly downregulated in non-progressive patients after FOLFIRINOX. In multivariate analysis, this decline correlated with improved PFS and overall survival, especially when combined with CA19-9 decline [hazard ratio (HR) = 0.153, 95% confidence interval (CI), 0.067-0.347 and HR = 0.201, 95% CI, 0.070-0.576, respectively]. This combination did not correlate with survival in patients treated with gemcitabine plus nab-paclitaxel. Tissue expression of miR-181a-5p reflected plasma levels. Inhibition of miR-181a-5p coupled with oxaliplatin exposure in pancreatic cell lines decreased cell viability. CONCLUSIONS:Plasma miR-181a-5p is a specific biomarker for monitoring FOLFIRINOX response. Decline in plasma miR-181a-5p and CA19-9 levels is associated with better prognosis after FOLFIRINOX and may be useful for guiding therapeutic choices and surgical exploration.

摘要

目的: 本研究的目的是确定血浆microRNA (miRNA) 生物标志物，用于分层和监测接受FOLFIRINOX治疗的局部晚期或转移性胰腺导管腺癌 (PDAC) 患者，并调查他们的功能角色。摘要背景数据: FOLFIRINOX已经成为晚期PDAC患者的标准疗法，可用于潜在的下消化道疾病。然而，只有一部分患者有反应，迫切需要生物标志物来指导决策。方法: 我们使用基于微阵列的分析，根据FOLFIRINOX后患者的无进展生存期 (PFS)，在化疗前和化疗后血浆样本中发现失调的miRNAs。在一个独立队列 (n = 43) 中验证了 9 个候选血浆miRNAs。最具区分度的血浆miRNA与临床病理因素和生存率相关，也在另外一个接受吉西他滨联合nab-紫杉醇治疗的队列中进行了研究。在匹配的肿瘤组织中进一步评价表达模式。体外研究探讨了其功能、关键下游基因靶点以及与 5-氟尿嘧啶、伊立替康和奥沙利铂的相互作用。结果: FOLFIRINOX术后非进展患者血浆miR-181a-5p显著下调。在多变量分析中，这种下降与改善的PFS和总生存期相关，特别是与CA19-9 下降相结合 [风险比 (HR) = 0.153，95% 置信区间 (CI)，分别为 0.067-0.347 和HR = 0.201，95% CI，0.070-0.576]。这种组合与吉西他滨联合白蛋白结合型紫杉醇治疗患者的生存率无关。MiR-181a-5p的组织表达反映了血浆水平。抑制胰腺细胞系中奥沙利铂暴露的miR-181a-5p降低细胞活力。结论: 血浆miR-181a-5p是监测FOLFIRINOX反应的特异性生物标志物。FOLFIRINOX术后血浆miR-181a-5p和CA19-9 水平下降与较好的预后相关，可能有助于指导治疗选择和手术探查。

期刊介绍

《ANNALS OF SURGERY》 (点击进入期刊详情)

英文简介 : Annals of Surgery is the official publication of the American Surgical Association, European Surgical Association, Southern Surgical Association, New York Surgical Society and the Philadelphia Academy of Surgery.

中文简介 : （来自Google、百度翻译）《外科年鉴》是美国外科学会、欧洲外科学会、南方外科学会、纽约外科学会和费城外科学会的官方出版物。

CIRCULATION RESEARCH 期刊中科院评价数据

新中科院分区

大类(学科)	小类(学科)	学科排名
医学	SURGERY (外科)	1/200

新发布的期刊年发文量

年度总发文量	年度论文发表量	年度综述发表量
299	288	11

总被引频次 :50355

特征因子 : 0.066690

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