Ovarian Cancer Detection Using H-NMR_Based Metabonomics

描述(由申请人提供)： 早期发现上皮性卵巢癌(EOC)的基本原理是诊断时的分期与生存率之间的关系。虽然少数被准确诊断为I期疾病的患者的5年存活率超过90%，但患有晚期疾病的女性患者的存活率只有15%-20%。因此，癌症风险评估和筛查的目标是在疾病的临床前阶段检测早期EOC，以便随后的治疗将降低疾病的发病率和死亡率。目前，在卵巢癌中还没有一种早期检测策略能够产生足够高的特异性和阳性预测值(PPV)，从而在普通人群或高危人群中广泛使用。因此，应探索新的方法，如功能基因组学、蛋白质组学和代谢组学，以区分早期卵巢癌患者和健康人。“代谢组学”使用血清的高分辨率核磁共振(1H-核磁共振)来分析数千种低分子代谢物。使用模式识别方法挖掘得到的复杂多参数数据集。我们假设血清代谢组学将在普通人群和高危人群中检测到早期卵巢早衰。为了验证这一假说，我们提出了三个具体目标：(I)比较1期卵巢癌患者、年龄匹配的健康对照组和其他妇科疾病女性中基于1H核磁共振的代谢组学模式；(Ii)研究1H-核磁共振代谢组学检测卵巢癌高危女性早期EOC的能力(来自纽约州布法罗Gilda Radner家族性卵巢癌登记中心)；(Iii)探索属于导致EOC和对照组代谢组差异的鉴别器类别的低分子代谢物。拟议的研究可能导致识别早期检测EOC的新生物标志物，并将在普通人群和高危人群中早期检测EOC的前瞻性研究中进一步评估这些标志物。

DESCRIPTION (provided by applicant): The rationale for early detection of epithelial ovarian cancer (EOC) is the relationship between stage at diagnosis and survival. Whereas the small proportion of patients with accurately diagnosed stage I disease have 5-year survival rates in excess of 90%, the survival rate for women with advanced disease is only 15-20%. Therefore, the goal of cancer risk assessment and screening is to detect early-stage EOC in the pre-clinical phase of disease, such that subsequent treatment will reduce disease morbidity and mortality. At present, there is no early detection strategy in EOC that results in sufficiently high specificity and positive predictive value (PPV) to be of widespread use to either the general or high-risk populations. Consequently, novel approaches such as functional genomics, proteomics and metabonomics should be explored to distinguish individuals with early stage EOC from healthy individuals. "Metabonomics" uses high-resolution nuclear magnetic resonance (1H-NMR) of serum to profile thousands of low-molecular-weight metabolites. The resulting complex multiparametric data sets are mined using pattern recognition methods. We hypothesize that serum metabonomics will detect early stage EOC in both the general and high-risk populations. In order to test this hypothesis, we propose three specific aims: (i) To compare 1HNMR based metabonomic patterns in women with stage 1 ovarian cancer, healthy age-matched controls, and women with other gynecologic conditions, (ii) To investigate the ability of 1H-NMR metabonomics to detect early EOC in women at high-risk for ovarian cancer (from the Gilda Radner Familial Ovarian Cancer Registry, Buffalo, NY), (iii) To explore the identification of the low-molecular weight metabolites that fall within the discriminator classes responsible for differences in metabonomic profiles between EOC and controls. The proposed studies may lead to the identification of novel biomarkers for early detection of EOC, that will be evaluated further in prospective studies for early detection of EOC in general and high-risk populations.