KALLIKREINS AS DIAGNOSTIC MARKERS OF OVARIAN CARCINOMA

描述（由申请人提供）：卵巢癌是一个主要的健康问题，也是最致命的妇科恶性肿瘤。虽然超过80%的患者在早期诊断时存活，但如果在晚期诊断，则超过75%的患者在5年内死亡。因此，尽早诊断和治疗卵巢癌至关重要。由于这种疾病相对罕见，因此生化检测必须具有非凡的特异性和敏感性。不幸的是，成熟的卵巢癌生物标志物CA125并不符合这些标准。在筛查情况下，CA125的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，无论是单独或组合，可以带来所需的灵敏度和特异性。我们在过去已经表明，许多成员的人激肽释放酶家族是有前途的新的生物标志物卵巢癌。更具体地，激肽释放酶hK5、hK6、hK7、hK8、hK10、hK11和hK14在初步临床研究中已显示出在诊断和预后中具有价值，并且它们中的一些可以补充CA 125。在本申请中，我们将详细研究，并与大量的样本，诊断的敏感性和特异性的一组卵巢癌生物标志物组成的CA 125，7上述激肽释放酶和其他六个有前途的分子。在这项工作中，我们确保了临床医生的参与，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中收集了大量特征良好的血清样本。在合作中，我们将使用申请人实验室开发的免疫荧光程序分析这些样本。统计分析将使我们能够a）开发最合适的多参数模型，以及B）建立复合测试的诊断灵敏度和特异性。我们希望这种新的组合将带来诊断的灵敏度和特异性，适用于筛查和早期诊断无症状患者。如前所述，我们的应用程序侧重于早期检测。这项研究与公共卫生的相关性：通过实现卵巢癌的早期诊断，可以通过尽早实施有效治疗来减轻疾病负担。

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.