Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, Australia.
Department of Obstetrics and Gynaecology, Royal North Shore Hospital, St. Leonards, Australia.
Gynecol Oncol. 2018 Jan;148(1):181-188. doi: 10.1016/j.ygyno.2017.11.005. Epub 2017 Nov 10.
The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management.
We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers.
We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818.
A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome.
对于高级别浆液性卵巢癌(HGSOC)患者的临床管理,最常用的方法是手术,随后是铂类和紫杉烷类为基础的化疗。手术结束时残留的宏观疾病程度是决定无进展和总生存期的关键预后因素。我们试图开发一种非侵入性测试来帮助外科医生确定实现完全手术切除的可能性。这方面的知识可以用于规划手术方法,以实现最佳的临床管理。
我们使用包含锁核酸(LNA)引物的 Serum/Plasma Focus miRNA PCR 面板(Exiqon)对 56 名 HGSOC 患者(N=56)和年龄匹配的健康志愿者(N=30)的 170 种血清 microRNAs(miRNAs)进行了分析。此外,我们还测量了同一批样本中的血清 CA-125 水平。根据手术结束时的宏观疾病程度,进一步对 HGSOC 队列进行分类。逐步逻辑回归用于识别预测标志物。
我们确定了 miR-375 和 CA-125 的组合是区分健康和 HGSOC 血清的最强指标,曲线下面积(AUC)为 0.956。miR-210 的加入增加了 AUC 至 0.984;然而,miR-210 受到溶血的影响。miR-34a-5p 和 CA-125 的组合是预测手术完全切除的最强预测因子,AUC 为 0.818。
一种包含循环 miRNA 的分子测试,用于预测 HGSOC 患者手术切除的完整性,有可能有助于规划最佳的患者管理,最终改善患者的预后。