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循环 miR-622 在初诊和复发性高级别浆液性卵巢癌患者中的预测相关性。

Predictive Relevance of Circulating miR-622 in Patients with Newly Diagnosed and Recurrent High-Grade Serous Ovarian Carcinoma.

机构信息

Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.

UNICANCER, Cancer Center F. Baclesse, Caen, France.

出版信息

Clin Chem. 2020 Feb 1;66(2):352-362. doi: 10.1093/clinchem/hvz013.

Abstract

BACKGROUND

Identifying patients with high-grade serous ovarian cancer (HGSOC) who will respond to treatment remains a clinical challenge. We focused on miR-622, a miRNA involved in the homologous recombination repair (HRR) pathway, and we assessed its predictive value in serum prior to first-line chemotherapy and at relapse.

METHODS

Serum miR-622 expression was assessed in serum prior to first-line platinum-based chemotherapy in a prospective multicenter study (miRNA Serum Analysis, miRSA, NCT01391351) and a retrospective cohort (Biological Resource Center, BRC), and was also studied at relapse. Progression-free survival (PFS) and overall survival (OS) were used as primary and secondary endpoints prior to first-line chemotherapy and OS as a primary endpoint at relapse.

RESULTS

The group with high serum miR-622 expression was associated with a significantly lower PFS (15.4 versus 24.4 months; adjusted HR 2.11, 95% CI 1.2 3.8, P = 0.015) and OS (29.7 versus 40.6 months; adjusted HR 7.68, 95% CI 2.2-26.2, P = 0.0011) in the miRSA cohort. In the BRC cohort, a high expression of miR-622 was also associated with a significantly lower OS (22.8 versus 35.9 months; adjusted HR 1.98, 95% CI 1.1-3.6, P = 0.026). At relapse, high serum miR-622 was associated with a significantly lower OS (7.9 versus 20.6 months; adjusted HR 3.15, 95% CI 1.4-7.2, P = 0.0062). Serum miR-622 expression is a predictive independent biomarker of response to platinum-based chemotherapy for newly diagnosed and recurrent HGSOC.

CONCLUSIONS

These results may open new perspectives for HGSOC patient stratification and monitoring of resistance to platinum-based and poly(ADP-ribose)-polymerase-inhibitor-maintenance therapies, facilitating better and personalized treatment decisions.

摘要

背景

识别对治疗有反应的高级别浆液性卵巢癌(HGSOC)患者仍然是一项临床挑战。我们专注于 miR-622,一种参与同源重组修复(HRR)途径的 miRNA,并评估了其在一线化疗前和复发时血清中的预测价值。

方法

在一项前瞻性多中心研究(miRNA 血清分析,miRSA,NCT01391351)和回顾性队列(生物资源中心,BRC)中,在一线基于铂的化疗前评估了血清 miR-622 的表达,并在复发时进行了研究。无进展生存期(PFS)和总生存期(OS)分别作为一线化疗前的主要和次要终点,OS 作为复发时的主要终点。

结果

血清 miR-622 高表达组的 PFS(15.4 与 24.4 个月;调整 HR 2.11,95%CI 1.2-3.8,P=0.015)和 OS(29.7 与 40.6 个月;调整 HR 7.68,95%CI 2.2-26.2,P=0.0011)明显降低。在 BRC 队列中,miR-622 的高表达也与 OS 明显降低相关(22.8 与 35.9 个月;调整 HR 1.98,95%CI 1.1-3.6,P=0.026)。在复发时,高血清 miR-622 与 OS 明显降低相关(7.9 与 20.6 个月;调整 HR 3.15,95%CI 1.4-7.2,P=0.0062)。血清 miR-622 表达是新诊断和复发性 HGSOC 患者对铂类化疗反应的独立预测生物标志物。

结论

这些结果可能为 HGSOC 患者分层和监测对铂类和聚(ADP-核糖)-聚合酶抑制剂维持治疗的耐药性开辟新的视角,从而促进更好和更个体化的治疗决策。

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