KALLIKREINS AS DIAGNOSTIC MARKERS OF OVARIAN CARCINOMA

激肽释放酶作为卵巢癌的诊断标志物

• 批准号: 7433273
• 负责人: ELEFTHERIOS P DIAMANDIS
• 金额: $ 21.69万
• 依托单位: SINAI HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433273
• 关键词: Abdomen; Age; Appendix; Applications Grants; Benign; Biochemical; Biological; Biological Assay; Biological Markers; Biotechnology; CA-125 Antigen; Canada; Cancer Center; Cancer Patient; Categories; Clinical; Clinical Research; Collaborations; Complement; Condition; Core Facility; Data; Databases; Development; Diagnosis; Diagnostic; Diagnostic Sensitivity; Disease; Doctor of Medicine; Early Detection Research Network; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Enzymes; Epidemiology; Evaluable Disease; Family; Fred Hutchinson Cancer Research Center; Funding; Genes; Goals; Grant; Health; Hospitals; Human; Human Glandular Kallikrein 2; Immunohistochemistry; Individual; Institution; Insulin-Like Growth Factor II; Intellectual Property; Japan; KLK15 Gene; KLK2 gene; Kininogenase; Laboratories; Leptin; Libraries; Licensing; Liquid substance; Literature; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Methodology; Methods; Modeling; Modification; Multicenter Studies; Multiparametric Analysis; New York; Numbers; Operative Surgical Procedures; Ovarian; Ovarian Carcinoma; Ovarian Cysts; Pathologist; Pathology; Patients; Phage Display; Physiological; Pilot Projects; Predictive Value; Principal Investigator; Private Sector; Procedures; Prolactin; Proteins; Public Health; Publishing; Race; Reagent; Receiver Operating Characteristics; Recombinant Proteins; Recording of previous events; Reproduction spores; Research; Research Institute; Resources; Retrospective Studies; Role; Sampling; Scientist; Score; Screening for Ovarian Cancer; Screening procedure; Secure; Sensitivity and Specificity; Series; Serum; Services; Slide; Somatomedins; Staging; Statistical Data Interpretation; Suggestion; Surgical Pathology; Symptoms; System; Technology; Testing; Tissue Sample; Tissues; Universities; Uterine Fibroids; WFDC2 gene; Woman; Women' s Health; Work; base; burden of illness; cancer diagnosis; cancer type; clinical Diagnosis; cohort; combinatorial; desire; endometriosis; experience; human kallikrein 14; human kallikrein 5; improved; kallikrein 4; medical schools; member; mesothelin; novel; osteopontin; outcome forecast; programs; response; tool

DESCRIPTION (provided by applicant): Ovarian cancer is a major health problem and the most lethal gynecological malignancy. While more than 80% of patients survive the disease when it is diagnosed early, more than 75% of patients die within 5 years if the disease is diagnosed at a late stage. Thus, it is crucial that ovarian cancer is diagnosed and treated as early as possible. Since the disease is relatively rare, the biochemical testing must be characterized by extraordinary specificity and sensitivity. Unfortunately, the well-established ovarian cancer biomarker, CA125, does not meet these criteria. Under a screening scenario, the positive predictive value of CA125 is unacceptable and well-below 10%. There is a need to identify novel ovarian cancer biomarkers which, either alone or in combination, can bring about the desired sensitivity and specificity. We have shown in the past that many members of the human kallikrein family are promising new biomarkers for ovarian carcinoma. More specifically, the kallikreins hK5, hK6, hK7, hK8, hK10, hK11 and hK14 have been shown in preliminary clinical studies to have value in diagnosis and prognosis and some of them can complement CA125. In this application, we will examine in detail, and with a large series of samples, the diagnostic sensitivity and specificity of a panel of ovarian cancer biomarkers consisting of CA125, the 7 aforementioned kallikreins and six other promising molecules. In this effort, we have secured the participation of clinicians who have collected a large series of well-characterized serum samples from ovarian cancer patients [early and late stage] as well as patients with benign gynecological diseases and normal controls. In collaboration, we will analyze these samples by using immunofluorometric procedures developed in the applicant's laboratory. Statistical analysis will allow us to a) develop the most appropriate multiparametric models and b) establish the diagnostic sensitivity and specificity of the composite test. We hope that this novel combination will bring about a diagnostic sensitivity and specificity that is suitable for screening and for early diagnosis of asymptomatic patients. As noted, our application focuses on early detection. Relevance of this research to public health: By achieving early ovarian cancer diagnosis, it will be possible to reduce the burden of the disease by administration of effective treatment as early as possible.

描述（申请人提供）：卵巢癌是主要的健康问题和最致命的妇科恶性肿瘤。在早期诊断时，80%以上的患者能存活，而在晚期诊断时，超过75%的患者会在5年内死亡。因此，卵巢癌的早期诊断和治疗是至关重要的。由于该病相对罕见，生化检测必须具有非凡的特异性和敏感性。不幸的是，公认的卵巢癌生物标志物CA125不符合这些标准。在筛查情景下，CA125阳性预测值是不可接受的，远低于10%。有必要确定新的卵巢癌生物标志物，无论是单独还是联合，都能带来所需的灵敏度和特异性。我们在过去的研究中已经表明，人类小肽激酶家族的许多成员是有希望的卵巢癌新生物标志物。更具体地说，hK5、hK6、hK7、hK8、hK10、hK11和hK14已在初步临床研究中显示具有诊断和预后价值，其中部分可作为CA125的补体。在这个应用中，我们将通过大量的样本，详细检查一组卵巢癌生物标志物的诊断敏感性和特异性，这些生物标志物包括CA125、前面提到的7种钾化酶和其他6种有前途的分子。在这项工作中，我们获得了临床医生的参与，他们从卵巢癌患者（早期和晚期）以及良性妇科疾病患者和正常对照患者中收集了大量具有良好特征的血清样本。在合作中，我们将使用申请人实验室开发的免疫荧光测定程序分析这些样品。统计分析将使我们能够a)开发最合适的多参数模型和b)建立复合测试的诊断敏感性和特异性。我们希望这种新颖的组合将带来诊断的敏感性和特异性，适合于筛查和早期诊断无症状的患者。如前所述，我们的应用程序侧重于早期检测。本研究与公共卫生的相关性：通过实现卵巢癌的早期诊断，将有可能通过尽早给予有效治疗来减轻疾病的负担。