BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
J Clin Oncol. 2019 Nov 20;37(33):3090-3098. doi: 10.1200/JCO.18.02057. Epub 2019 Sep 25.
Our objective was to evaluate operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumor.
One hundred eleven male patients with a history of or newly diagnosed germ cell tumors were evaluable. Biospecimens obtained before confirmed clinical events were analyzed for miR371 expression with blinding of providers and laboratory personnel to analytic results or clinical status, respectively. Cases (patients with clinically confirmed active germ cell malignancy [aGCM]) and controls (patients with no clinically confirmed aGCM) were assigned over the course of the management. Patients were assigned risk status (high, low, or moderate) based on the composite clinical picture at time points in management.
Considering all cases and controls and results of prospectively obtained biosamples analyzed for miR371 expression, 46 (35%) of 132 samples had clinically confirmed aGCM over the course of management; 44 (96%) of these 46 patients had plasma miR371 expression (true positives) with no false positives. Two (4%) of 46 patients had no miRNA expression despite pathologic confirmation of aGCM (false negatives). Plasma miR371 expression in confirmed aGCM had a specificity, sensitivity, positive predictive value, and negative predictive value of 100%, 96%, 100%, and 98%, respectively. Interpretation of sensitivity and negative predictive value is limited by modest follow-up. Specificity and sensitivity were 100% and 98%, 100% and 92%, and 100% and 97% in the low-, moderate-, and high-risk groups, respectively, with a median follow-up time of 15 months.
Plasma miR371 expression predicts aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 await longer follow-up for more complete definition, the findings of a highly specific liquid biopsy strongly support moving forward with large-scale, real-world clinical trials to further define full operating characteristics and to identify clinical utility and areas of patient benefit.
通过将血浆 miR371 表达与有生殖细胞瘤病史患者的实际临床事件进行映射，评估其检测特征，尤其是特异性和阳性预测值（PPV）。
111 名有生殖细胞瘤病史或新诊断为生殖细胞瘤的男性患者可进行评估。在获得生物样本后，对提供者和实验室人员分别进行 miR371 表达分析，分析时对分析结果或临床状况均设盲。根据临床确认的生殖细胞恶性肿瘤（aGCM）的实际情况，将病例（临床确认的活动性生殖细胞恶性肿瘤患者）和对照（无临床确认的 aGCM 患者）分配。根据管理过程中各时间点的综合临床情况，患者被分配为高、中、低风险状态。
考虑到所有病例和对照以及前瞻性分析 miR371 表达的生物样本的结果，在管理过程中，132 个样本中有 46 个（35%）被临床确认为 aGCM；这 46 例患者中有 44 例（96%）有血浆 miR371 表达（真阳性），无一例假阳性。尽管病理证实为 aGCM，但仍有 2 例（4%）患者无 miRNA 表达（假阴性）。在确认的 aGCM 中，血浆 miR371 表达的特异性、敏感性、阳性预测值和阴性预测值分别为 100%、96%、100%和 98%。由于随访时间有限，对敏感性和阴性预测值的解释有限。在低危、中危和高危组中，特异性和敏感性分别为 100%和 98%、100%和 92%、100%和 97%，中位随访时间为 15 个月。
血浆 miR371 表达可预测 aGCM，具有高特异性和阳性预测值。尽管 miR371 的其他检测特征有待更长时间的随访以更完整地定义，但这种高特异性液体活检的发现强烈支持开展大规模真实世界临床试验，以进一步确定其完整的检测特征，并确定其临床应用价值和患者获益领域。
