A Novel Approach for the Routine Screening for Ovarian Cancer

卵巢癌常规筛查的新方法

• 批准号: 8551644
• 负责人: Lewis K. Pannell
• 金额: $ 39.97万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-26 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8551644
• 关键词: Accounting; Adnexal Mass; Belief; Benign; Biological Markers; Blood; CA-125 Antigen; Cancer Detection; Cancer Patient; Cause of Death; Cells; Cervical; Cervix Mucus; Cervix Uteri; Cessation of life; Clinic; Clinical; Clinical Data; Collection; Computer software; Data; Development; Diagnosis; Disease; Early Diagnosis; Enrollment; Epithelial ovarian cancer; Female; Fingerprint; General Population; Goals; Gynecologic; Gynecologic Oncologist; Gynecologic Oncology; Histology; Institutes; Institutional Review Boards; Legal patent; Liquid substance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mass Spectrum Analysis; Measurement; Medically Underserved Area; Methods; Molecular; Monitor; Mucous body substance; Newly Diagnosed; Oocytes; Organ; Ovarian; Ovary; Papillary; Patients; Peptides; Peritoneal Fluid; Peritoneum; Phase; Physicians; Procedures; Process; Prospective Studies; Proteins; Proteomics; Publications; Qualifying; Reaction; Research; Research Personnel; Rest; Sample Size; Sampling; Screening for Ovarian Cancer; Self-Administered; Sensitivity and Specificity; Serous; Serum; Site; Source; Specificity; Staging; Statistical Data Interpretation; Surface; Survival Rate; Symptoms; System; Techniques; Testing; Time; Uterine cavity; Uterus; Vagina; Validation; Visit; Work; base; cervicovaginal; cohort; design; egg; female reproductive system; high risk; novel; novel strategies; outcome forecast; protein profiling; protein transport; research facility; rural area; sample collection; screening; tool; validation studies; wasting

DESCRIPTION (provided by applicant): Ovarian cancer is deadly and generally diagnosed at late stage when the chances of survival are low. There is a current belief that this cancer starts in the fallopian tubes and progresses towards the ovaries, spreading to the cells on the surface. The ovaries are somewhat engulfed in the ends of the fallopian tubes which are designed to capture what is released and transport this into the uterus. While designed to capture the released eggs, the flow created by the follicles will also capture the released proteins and transport them towards the uterine cavity. Within the fallopian tubes and the uterus, there is a constant flow of mucus which has only one exit through the cervix and out the vagina. Proteins that are generated within the entire female reproductive system are trapped into this viscous fluid and eventually released as waste. When a routine PAP test is performed, a sample of this mucus is collected along with any cells, and preserved in the PAP fluid. The fluid is currently discarded but contains a protein profile showing of the status of the cells in the female reproductive system. We have examined this fluid and found that it contains unique peptides/proteins that provide a diagnosis of ovarian cancer when compared against healthy controls. These markers will be initially refined using the comparison of ovarian cancer patients against those with benign adnexal masses that entered the clinic during the same time period. In this Phase II biomarker validation study we will further refine and validate these biomarkers using a new collection of samples from at least 200 ovarian cancer cases with epithelial ovarian cancer (endometroid and papillary serous histology, most common) and comparing these against 600 patients with a diagnosis of a benign adnexal mass that enter the clinics during the same time period. Patient samples will be collected on their first visit to the gynecologic oncologist at a number of collaborating clinics. Final processing of all of the samples will be performed within the proteomics research facilities of the Mitchell Cancer Institute using Selected Reaction Monitoring (SRM, with mass spectrometry) based on the refined set of makers statistically selected within the first aim. We have been working on this approach and collecting samples for four years and filed patents on the approach. Cervicovaginal fluid offers a high enriched sample for discovery and diagnosis of gynecological cancers. Biomarkers validated within this study will be compared with the well accepted CA-125 data for the patients. The potential early detection of ovarian cancer in this restricted proteomic sample is only enhanced by the current belief that ovarian cancer may originate in the fallopian tubes. The research involves a three year validation and may allow detection of this cancer at a very early stage when the survival is as high as 90%. One aim examines a self-taken test that could allow its use in medically underrepresented and rural areas.

描述(申请人提供)：卵巢癌是致命的，通常在生存机会低的晚期被诊断出来。目前有一种观点认为，这种癌症始于输卵管，并向卵巢扩散，扩散到体表的细胞。卵巢在一定程度上被吞噬在输卵管的末端，输卵管的设计是为了捕捉释放的东西并将其输送到子宫中。虽然设计用于捕获释放的卵子，但由卵泡产生的流动也将捕获释放的蛋白质并将其输送到子宫腔。在输卵管和子宫内，有源源不断的粘液流动，只有一个出口通过宫颈并流出阴道。在整个女性生殖系统中产生的蛋白质被困在这种粘性液体中，最终以废物的形式释放。当进行常规的PAP检测时，这种粘液的样本与任何细胞一起被收集，并保存在PAP液中。这种液体目前被丢弃，但含有显示女性生殖系统中细胞状态的蛋白质图谱。我们检查了这种液体，发现它含有独特的多肽/蛋白质，与健康对照组相比，这些多肽/蛋白质可以提供卵巢癌的诊断。这些标记物最初将通过比较卵巢癌患者和同期进入临床的良性附件肿块患者进行提炼。在这项II期生物标记物验证研究中，我们将使用从至少200例卵巢癌上皮性癌(最常见的是子宫内膜样癌和乳头状浆液性组织学)中收集的新样本，进一步提炼和验证这些生物标记物，并将这些样本与同期进入临床的600名被诊断为良性附件肿块的患者进行比较。患者的样本将在他们第一次去一些合作诊所的妇科肿瘤学家那里就诊时收集。所有样本的最终处理将在米切尔癌症研究所的蛋白质组学研究设施内使用选择反应监测(SRM，带质谱学)进行，该监测基于在第一个目标内统计选择的一组精细化的标志物。我们一直在研究这种方法，并收集了四年的样本，并为这种方法申请了专利。宫颈阴道液为妇科癌症的发现和诊断提供了高度浓缩的样本。在这项研究中验证的生物标记物将与患者接受的CA-125数据进行比较。只有目前认为卵巢癌可能起源于输卵管的观点，才能加强这种受限蛋白质组样本早期发现卵巢癌的可能性。这项研究涉及三年的验证，可能会在存活率高达90%的非常早期阶段发现这种癌症。其中一个目标是检查一种自我测试，这种测试可能允许在医疗代表性不足的农村地区使用它。