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: 10590574
• 负责人: Lucia Nappi
• 金额: $ 38.3万
• 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/10590574
• 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; Epigenetic Process; Family; Germ Cells; Germ cell tumor; Gonadal structure; Image; Individual; International; Intervention; 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; Solid; Southwest Oncology Group; Specificity; Specimen; Statistical Data Interpretation; 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 predictive model; cohort; cost; cost effective; design; diagnostic biomarker; early detection biomarkers; embryonic stem cell; follow-up; gonad development; improved; innovation; overexpression; overtreatment; participant enrollment; patient oriented; patient population; pluripotency; pre-clinical; predictive modeling; prenatal; prevent; primary endpoint; prospective; radiological imaging; repository; side effect; standard of care; statistics; 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miRNA尚未证明是容易的治疗靶标，但越来越多的证据 表明它们是生殖细胞肿瘤（GCT）中可靠的诊断生物标志物。 GCT是胚胎的， 在生物学上与其他固体恶量非常不同，并保留大多数胚胎干细胞 特征，包括特定子集的miRNA。 miR371a-3p（miR371）具有很高的精度 鉴定精子瘤和非肿瘤瘤GCT中的活性生殖细胞恶性肿瘤（AGCM）。为了移动 这种生物标志物进入临床实践，已经设计了2个临床试验，目前正在累计 小儿（AGCT-1531）和成年GCT种群（S1823）的患者。 S1823是一项震惊的队列试验 这具有前瞻性和临床验证成人GCT中的miR371的目标。 利用我们在S1823中的小组领导职位，我们建议使用等离子Mir371 表达数据和放射学图像以及为S1823收集的临床数据结合以创建生物学 在监视时，早期GCT患者AGCM的临床预测模型。 假设。 MIR371的PPV高于标准的临床工具，可以在早期胚芽中识别AGCM 细胞肿瘤，可以用来更早地鉴定肿瘤继电器。 目标。该研究项目的目的是： 1。测量基线和随访期间S1823标本中的等离子体miR371表达。 2。整合/将定性和定量miR371表达与临床注释进行了比较 在S1823试验设计中。 方法。监视期间收集的基线和连续样品的招募患者 S1823将使用RT-PCR分析MIR371的表达。在同一收集的CT扫描图像数据 MiR371的时间点将与MiR371表达进行比较，以测定PPV，NPV，灵敏度 和特异性。分析测试的准确性将进行分析以定义 ROC并创建一个整合临床和生物学数据的AGCM的预测模型。 创新。该研究建议的创新既不存在于完全基本和通用的RT-PCR中 用于miR371表达的技术，也不是简单的统计和研究设计。创新包括 在这种高度特异的生物学标记物的潜在临床利用中，以早期检测AGCM 为替换或整合传统图像，治疗降低和整合更多机会 在生物学基础上的个性化，而不是GCT的临床证据。 意义和影响：监视期间对AGCM的早期，更准确的识别具有 减少年轻GCT患者人群的治疗燃烧的潜力并预防长期的治疗 GCT患者生活质量的有意义改善，化学疗法和辐射治疗的影响。