MicroRNA biomarkers for early detection of prostate cancer

用于前列腺癌早期检测的 MicroRNA 生物标志物

• 批准号: 7538186
• 负责人: DAVID M BROWN
• 金额: $ 21.56万
• 依托单位: AMBION DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538186
• 关键词: Address; Age; American; Benign Prostatic Hypertrophy; Biological Assay; Biological Markers; Cancer Etiology; Cancer Patient; Caregivers; Caring; Cells; Cessation of life; Clinic; Clinical; Computer Analysis; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Management; Drops; Grant; Individual; Laboratories; Lead; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measures; Metastatic Prostate Cancer; Methods; MicroRNAs; Molecular; Molecular Diagnostic Testing; Monitor; Numbers; Patients; Phase; Pilot Projects; Plasma; Predictive Value; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Public Health; RNA; Rate; Receiver Operator Characteristics; Research; Sampling; Screening for Prostate Cancer; Screening for cancer; Screening procedure; Serum; Small RNA; Specificity; Staging; Survival Rate; System; Testing; Uncertainty; United States; United States Food and Drug Administration; Validation; Work; assay development; base; cancer diagnosis; digital; improved; male; man; men; mortality; mouse model; normal aging; programs; prostatitis; rectal; research clinical testing; tumor; vigilance

DESCRIPTION (provided by applicant): Prostate cancer (PrCa) is the most commonly diagnosed cancer in American men, with over 218,000 new cases diagnosed each year. It is second only to lung cancer in cancer mortality among men, and approximately 1 man in 5 will be diagnosed during his lifetime. When it is detected early, PrCa can be cured. In contrast, patients with metastatic prostate cancer have very low survival rates. The early and accurate diagnosis of PrCa patients is critical for the successful management of the disease. While prostate specific antigen testing (PSA) and digital rectal exam have improved the care of PrCa patients, the false positive and false negative rates of the PSA test limit its applicability for many patients. Diagnostic assays that can overcome the shortcomings of the PSA tests would be welcomed by both caregivers and patients. In this project we will explore the development of a microRNA (miRNA)-based diagnostic test for PrCa that can be used in combination with PSA to provide more accurate cancer screening. We have developed methods to isolate and detect miRNAs in biofluids. Our preliminary data indicated that these are stable, easy to detect and differentially expressed in the circulating biofluids of PrCa patients. In Aim 1 of this proposal we will test a panel of miRNA biomarkers, identified from our initial studies, for their ability to differentiate PrCa patients, patients with benign prostatic hyperplasia and normal aged matched controls. In Aim 2 we will use Asuragen's DiscovArray miRNA microarray system to expand our miRNA discovery to find biomarker candidates that can be used with PSA to distinguish hard to resolve clinical samples. We anticipate that the completed studies will lead to the development of simple molecular diagnostic assay that can be used in the clinic. Phase II of this grant would address more rigorous validation of the biomarker set using samples collected at clinical laboratories. Additionally, we will explore further the idea that a miRNA-based assay may have high predictive value in the absence of PSA information. Following successful validation, we will explore optimization of qRT-PCR parameters and relevant controls for assembling an assay for clinical testing. PUBLIC HEALTH RELEVANCE:Prostate cancer continues to be the second leading cause of cancer deaths in males despite the availability of simple clinical screening tests. Our work may lead to the development of cutting-edge microRNA-based molecular diagnostic tests that can be combined with current clinical tests to provide more accurate detection of early prostate cancer and reduce the number of deaths due to prostate cancer.

描述（由申请人提供）：前列腺癌（PRCA）是美国男性最常见的癌症，每年诊断出218,000例新病例。它仅次于男性癌症死亡率的肺癌，在他的一生中将被诊断出5名男性。早期检测到它时，可以治愈PRCA。相反，转移性前列腺癌的患者的存活率非常低。 PRCA患者的早期诊断对于成功治疗该疾病至关重要。尽管前列腺特异性抗原测试（PSA）和数字直肠检查改善了PRCA患者的护理，但PSA测试的假阳性和假阴性率限制了其对许多患者的适用性。可以克服PSA测试缺点的诊断测定方法将受到护理人员和患者的欢迎。在这个项目中，我们将探索用于PRCA的MicroRNA（miRNA）诊断测试的开发，该测试可与PSA结合使用，以提供更准确的癌症筛查。我们开发了分离和检测生物流体中miRNA的方法。我们的初步数据表明，在PRCA患者的循环生物流体中，它们稳定，易于检测和差异表达。在该提案的目标1中，我们将测试一组miRNA生物标志物，从我们的初步研究中确定，以区分PRCA患者，良性前列腺增生和正常老年匹配对照的患者的能力。在AIM 2中，我们将使用Asuragen的Discovarray miRNA微阵列系统来扩展我们的miRNA发现，以找到可与PSA一起使用的生物标志物候选者，以区分难以解决临床样品。我们预计完成的研究将导致可以在诊所中使用的简单分子诊断测定法的发展。该赠款的第二阶段将使用在临床实验室收集的样品对生物标志物集的更严格验证。此外，我们将进一步探讨以下观点：基于miRNA的测定在没有PSA信息的情况下可能具有高预测价值。成功验证后，我们将探索QRT-PCR参数和相关控制的优化，以组装用于临床测试的测定法。公共卫生相关性：尽管有简单的临床筛查测试可用，但前列腺癌仍然是男性癌症死亡的第二大原因。我们的工作可能导致开发基于尖端的microRNA分子诊断测试，这些测试可以与当前的临床测试结合使用，以提供对早期前列腺癌的更准确检测，并减少因前列腺癌而导致的死亡人数。