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（由申请人提供）：卵巢癌是致命的，通常在晚期诊断时，生存的机会很低。目前有一种观点认为，这种癌症始于输卵管，并向卵巢发展，扩散到表面的细胞。卵巢在某种程度上被输卵管的末端所吞没，输卵管的目的是捕获释放的物质并将其运送到子宫中。虽然设计用于捕获释放的卵子，但卵泡产生的流动也将捕获释放的蛋白质并将其运送到子宫腔。在输卵管和子宫内，粘液不断流动，只有一个出口，通过子宫颈和阴道。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，最终作为废物释放出来。当进行常规PAP试验时，将该粘液的样品与任何细胞一起收集沿着，并保存在PAP流体中。这些液体目前被丢弃，但含有显示女性生殖系统细胞状态的蛋白质谱。我们检查了这种液体，发现它含有独特的肽/蛋白质，与健康对照相比，可以诊断卵巢癌。这些标志物最初将通过比较卵巢癌患者与同期进入诊所的良性附件肿块患者来完善。在这项II期生物标志物验证研究中，我们将进一步完善和验证这些生物标志物，使用来自至少200例上皮性卵巢癌（子宫内膜样和乳头状浆液性组织学，最常见）的卵巢癌病例的新样本，并将这些样本与600例诊断为良性附件肿块的患者进行比较，这些患者在同一时间段进入诊所。患者样本将在其首次就诊于多家合作诊所的妇科肿瘤医生时采集。所有样品的最终处理将在Mitchell癌症研究所的蛋白质组学研究设施内进行，使用基于在第一个目标内统计选择的标记物的精细集合的选择反应监测（SRM，具有质谱法）。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。宫颈阴道液为妇科肿瘤的发现和诊断提供了高浓度的样本。将本研究中验证的生物标志物与患者公认的CA-125数据进行比较。目前认为卵巢癌可能起源于输卵管，这一限制性蛋白质组样本中卵巢癌的潜在早期检测仅得到加强。该研究涉及三年的验证，并可能在生存率高达90%的早期阶段检测到这种癌症。其中一个目的是研究一种自我测试，可以让它在医学代表性不足和农村地区使用。