Integrative Metabolomics of Prostate Cancer Progression

前列腺癌进展的综合代谢组学 前列腺癌在西方世界的老年男性中是一种高度流行的疾病。多重复合体 前列腺癌的启动、不受调控的生长、侵袭和 转移。破译区分进展性疾病和非进行性疾病的分子网络 进行性疾病将揭示侵袭性前列腺癌和铅的生物学 用于识别有助于选择应接受治疗的患者的生物标志物。 利用微阵列对前列腺癌的基因表达谱进行了广泛的研究，并对 在广度和深度较小的情况下，使用质谱仪对前列腺肿瘤进行蛋白质组学分析也 已经被探索过了。相比之下，在新陈代谢组学方面所做的工作很少。 前列腺癌，它可能会提供比 传统的转录组学和蛋白质组学。MRNA表达或蛋白质的细微变化 功能/活性可能表现为特定代谢物浓度的巨大变化 从而对扰动进行更灵敏的检测。代谢物的全球图谱 前列腺癌将增强我们对在治疗过程中发生的通路改变的理解 疾病进展，并可能导致新的生物标记物和途径的开发 目标。目前的提案围绕着丰富的前列腺代谢谱概要 将被挖掘以定义特定类别以及致命或侵略性代谢体的组织 前列腺癌进展的标志物。因此，这项提案的首要目标是界定 并验证前列腺癌进展的临床相关代谢组标志物的子集 并确定它们在预测侵袭性疾病方面的有效性。有鉴于此，目标如下： 具体目标1：描述前列腺癌进展的潜在代谢标志物。 具体目标2：确定致命新陈代谢的预测/因果/结果作用 前列腺癌标记物的临床前肿瘤侵袭模型。 特定目标3：前列腺癌候选代谢生物标记物的临床相关性 进展性前列腺癌是美国癌症相关死亡的第二大原因。这种疾病经常是 如果及早发现是可以治愈的，而转移性疾病往往是致命的。此外，有一个迫在眉睫的 由于前列腺癌的特异性较低，需要为前列腺癌检测定义更多的生物标志物 前列腺特异性抗原(PSA)是目前用于早期检测的临床标准。《长河》 本提案的术语目标是定义临床相关代谢组标志物的子集和 使用有效的前列腺癌来确定它们与疾病进展过程的关系 动物模型。我们希望对前列腺癌进行如此系统的分子分析 代谢物将导致鉴定有朝一日可能成为靶点的途径改变 心理治疗。此外，随着将这些标记物过渡到临床环境的最终目标， 我们打算通过其他与前列腺相关的临床生物标本来验证它们。

TITLE: Integrative Metabolomics of Prostate Cancer Progression Prostate cancer is a highly prevalent disease in older men of the Western world. Multiple complex molecular events characterize prostate cancer initiation, unregulated growth, invasion, and metastasis. Deciphering the molecular networks that distinguish progressive disease from non- progressive disease will shed light into the biology of aggressive prostate cancer as well as lead to the identification of biomarkers that will aid in the selection of patients that should be treated. Gene expression profiling of prostate cancer by microarrays has been done extensively and to a lesser extent and depth, proteomic profiling of prostate tumors using mass spectrometry has also been explored. By contrast, very little has been done in the area of metabolomic profiling of prostate cancer, which may provide additional information content beyond that available from conventional transcriptomics and proteomics. Subtle alterations in mRNA expression or protein function/activity may manifest as an enormous change in the concentration of specific metabolites resulting in a more sensitive detection of the perturbation. Global profiling of the metabolites in prostate cancer will enhance our understanding of the pathway alterations occurring during disease progression and could lead to the development of novel biomarkers and pathways to target. The current proposal around a rich compendium of metabolomic profiles of prostate tissues that would be mined to define class-specific as well as lethal or aggressive metabolomic markers of prostate cancer progression. Thus the overarching goal of this proposal is to define and validate a subset of clinically relevant metabolomic markers of prostate cancer progression and determine their utility in predicting aggressive disease. Given this, the aims are as follows: Specific Aim 1: Delineate Potential Metabolomic Markers of Prostate Cancer Progression. Specific Aim 2: Establish the Predictive/Causal/Consequential Role for the Lethal Metabolomic Markers of Prostate Cancer Using Preclinical Models of Cancer Invasion. Specific Aim 3: Clinical Association of Candidate Metabolomic Biomarkers of Prostate Cancer Progression Prostate cancer is the second largest cause of cancer-related death in US. The disease is often curable if detected early, while metastatic disease is often fatal. Furthermore, there is an imminent need to define additional biomarkers for prostate cancer detection owing to the low specificity of prostate specific antigen (PSA), the current clinical standard used for its early detection. The long term goal of this proposal is to define a subset of clinically relevant metabolomic markers and define their association with the process of disease progression using validated prostate cancer animal models. Our hope is that such a systematic molecular analysis of prostate cancer metabolites would lead to identification of pathway alterations that could be one day targeted for therapy. Further, with the ultimate objective of transitioning these markers to the clinical setting, we intent to validate them across additional prostate-related clinical biospecimens.