Integrating investigational miR371a-3p with conventional radiology imaging for earlier and more precise detection of active germ cell malignancy: A BCC/SWOG/S1823 secondary use of data collaboration.

将研究性 miR371a-3p 与传统放射学成像相结合，以更早、更精确地检测活动性生殖细胞恶性肿瘤：BCC/SWOG/S1823 数据协作的二次使用。

• 批准号: 10312663
• 负责人: Lucia Nappi
• 金额: $ 42.33万
• 依托单位: PROVINCIAL HEALTH SERVICES AUTHORITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10312663
• 关键词: Adolescent and Young Adult; Adult; Back; Behavior; Biological; Biological Assay; Biological Markers; Biometry; Blood Tests; Cell Cycle Regulation; Characteristics; Childhood; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical assessments; Collaborations; Communities; Consensus; Coupled; Data; Detection; Development; Diagnosis; Division of Cancer Prevention; Embryonic Development; Enrollment; Epigenetic Process; Family; Germ Cells; Germ cell tumor; Gonadal structure; Image; Individual; International; Intervention; Investigation; Lead; Lesion; Liquid substance; Malignant Neoplasms; Measures; Methodology; Methods; MicroRNAs; Molecular; Nonseminomatous; North America; Patients; Plasma; Play; Population; Positioning Attribute; Post-Transcriptional Regulation; Pregnancy; Process; Puberty; Quality of life; Radiation therapy; Relapse; Research Design; Research Project Grants; Research Proposals; Resource-limited setting; Reverse Transcriptase Polymerase Chain Reaction; Role; Sampling; Seminoma; Sensitivity and Specificity; Ships; Small RNA; Solid; Southwest Oncology Group; Specificity; Specimen; Statistical Data Interpretation; Statistical Study; Survivors; Techniques; Testing; Time; Tissues; Toxic effect; Tumor Markers; Untranslated RNA; X-Ray Computed Tomography; base; biobank; cancer care; care delivery; clinical care; clinical investigation; clinical practice; clinical predictors; cohort; cost; cost effective; design; diagnostic biomarker; early detection biomarkers; embryonic stem cell; follow-up; gonad development; innovation; overexpression; overtreatment; patient oriented; patient population; pluripotency; pre-clinical; predictive modeling; prenatal; prevent; primary endpoint; prospective; radiological imaging; repository; side effect; standard of care; stem cells; therapeutic target; tool; trial design; tumor; unnecessary treatment; virtual

Project Summary Background. While miRNAs have not demonstrated to be easy therapeutic targets, growing evidence suggests that they are reliable diagnostic biomarkers in germ cell tumors (GCTs). GCTs are embryonally and biologically very distinct from other solid malignancies and retain most of the embryonal stem cells characteristics, including expression of a specific subset of miRNAs. miR371a-3p (miR371) has high accuracy to identify active germ cell malignancy (aGCM) in both seminoma and nonseminoma GCTs. In order to move this biomarker forward into the clinical practice, 2 clinical trials have been designed and are currently accruing patients in the pediatric (AGCT-1531) and adult GCT populations (S1823). S1823 is a SWOG-lead cohort trial that has the objective to prospectively and clinically validate miR371 in adult GCT. Taking advantage of our group leader position in S1823, we are proposing to utilize the plasma miR371 expression data and the radiologic images coupled with clinical data collected for S1823 to create a biological- clinical predictive model of aGCM in patients with early stage GCT on surveillance. Hypothesis. miR371 has higher PPV than standard of care clinical tools to identify aGCM in early stage germ cell tumors and it can be used to identify tumor relapse earlier and with more accuracy. Aims. The aims of this research project are to: 1. Measure plasma miR371 expression in S1823 specimens at baseline and during the follow-up. 2. Integrate/compare the qualitative and quantitative miR371 expression with the clinical annotation as detailed in the S1823 trial design. Methods. The baseline and the serial samples collected during the surveillance from the patients enrolled in S1823 will be analyzed for miR371 expression using RT-PCR. The CT scan images data collected at the same time point of miR371 will be compared to miR371 expression for the determination of the PPV, NPV, sensitivity and specificity. The accuracy of the tests individually or combined will be analyzed to define the AUC of the ROC and to create a predictive model of aGCM that integrates clinical and biological data. Innovation. The innovation of this research proposal resides neither in the quite basic and universal RT-PCR technique used for the miR371 expression, nor in the simple statistic and study design. The innovation consists in the potential clinical utilization of this highly specific biological marker for early detection of aGCM which will open more opportunities for replacement or integration of conventional images, treatment de-escalation and personalization on the base of biological rather than clinical evidence of GCTs. Significance and impact: Early and more accurate identification of aGCM during surveillance has the potential to reduce treatment burden of the young GCT patients’ population and to prevent long term side effects of chemo and radiation treatments with meaningful improvement of GCT patients’ quality of life.

项目摘要 背景虽然miRNAs还没有被证明是容易的治疗靶点，但越来越多的证据表明， 表明它们是生殖细胞肿瘤（GCT）的可靠诊断生物标志物。GCT是胚胎性的， 在生物学上与其他实体恶性肿瘤非常不同，并保留了大部分胚胎干细胞 特征，包括特定miRNA子集的表达。miR 371 a-3 p（miR 371）具有高准确度 以确定活跃的生殖细胞恶性肿瘤（aGCM）在卵巢癌和非卵巢癌GCT。为了移动 这种生物标志物已进入临床实践，目前已设计并正在进行2项临床试验 儿童（AGCT-1531）和成人GCT人群（S1823）中的患者。S1823是一项SWOG-lead队列试验 其目的是在成人GCT中前瞻性和临床验证miR 371。 利用我们在S1823中的小组领导地位，我们提议利用血浆miR 371 表达数据和放射学图像与为S1823收集的临床数据相结合，以创建生物- 监测中早期GCT患者aGCM的临床预测模型。 假说. miR 371具有比标准护理临床工具更高的PPV，以鉴定早期细菌中的aGCM 细胞肿瘤，可用于更早和更准确地识别肿瘤复发。 目标。该研究项目的目的是： 1.在基线和随访期间测量S1823标本中的血浆miR 371表达。 2.将定性和定量miR 371表达与详细的临床注释整合/比较 在S1823试验设计中。 方法.基线和监测期间从入组的患者中收集的系列样本 使用RT-PCR分析S1823的miR 371表达。CT扫描图像数据收集在同一时间， 将miR 371的时间点与miR 371表达进行比较，以确定PPV、NPV、灵敏度 和特异性。将分析单独或组合测试的准确度，以定义 ROC，并创建整合临床和生物学数据的aGCM预测模型。 创新本研究方案的创新之处既不在于十分基础和通用的RT-PCR 用于miR 371表达的技术，也不用于简单的统计和研究设计。创新包括 在这种高度特异性的生物标记物用于早期检测aGCM的潜在临床应用中， 为传统影像的替换或整合、治疗降级和 基于GCT的生物学而非临床证据的个性化。 意义和影响：在监测期间早期和更准确地识别aGCM， 有可能减轻年轻GCT患者人群的治疗负担，并预防长期副作用 化疗和放疗的效果，有意义的改善GCT患者的生活质量。