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。虽然一小部分准确诊断为I期疾病的患者的5年生存率超过90%，但晚期疾病妇女的生存率仅为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，以便后续治疗将降低疾病的发病率和死亡率。目前，在EOC中没有早期检测策略，其导致足够高的特异性和阳性预测值（PPV）以广泛用于一般或高危人群。因此，新的方法，如功能基因组学，蛋白质组学和代谢组学应探索区分个体与健康的早期EOC。“代谢组学”使用血清的高分辨率核磁共振（1H-NMR）来分析数千种低分子量代谢物。所产生的复杂的多参数数据集挖掘使用模式识别方法。我们假设，血清代谢组学将检测早期EOC的一般和高危人群。为了验证这一假设，我们提出了三个具体目标：（i）比较患有1期卵巢癌的女性、健康年龄匹配的对照和患有其他妇科疾病的女性中基于1HNMR的代谢组学模式，（ii）研究1H-NMR代谢组学检测卵巢癌高危女性中早期EOC的能力（来自Gilda Radner家族性卵巢癌登记处，布法罗，NY），（iii）探索属于导致EOC和对照之间代谢组学谱差异的代谢物类别的低分子量代谢物的鉴定。拟议的研究可能导致识别用于早期检测EOC的新生物标志物，将在一般和高危人群中进行EOC早期检测的前瞻性研究中进一步评估。

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.