Normandie Université, UNICAEN, Inserm U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, France.
UNICANCER, Cancer Center F. Baclesse, Caen, France.
Clin Chem. 2020 Feb 1;66(2):352-362. doi: 10.1093/clinchem/hvz013.
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.
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.
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.
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.
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。
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。
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。
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。