Metabolomic profiling of adolescent endometriosis

青少年子宫内膜异位症的代谢组学分析

• 批准号: 10524832
• 负责人: Naoko Sasamoto
• 金额: $ 31.33万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10524832
• 关键词: Adolescence; Adolescent; Adult; Affect; Arachidonic Acids; Biological; Biological Markers; Blood; CA-125 Antigen; Chronic Disease; Clinical; Color; Data; Diagnosis; Diagnostic; Disease; Dysmenorrhea; Early Diagnosis; Early Intervention; Economic Burden; Environment; Environmental Risk Factor; Functional disorder; Future; Genetic; Genome; Goals; Infertility; Lead; Lecithin; Lesion; Life Cycle Stages; Longitudinal cohort; Lysophosphatidylcholines; Machine Learning; Measurement; Measures; Metabolic Pathway; Molecular; Molecular Profiling; National Institute of Child Health and Human Development; Operative Surgical Procedures; Outcome; Pain; Pathway interactions; Patients; Pelvic Pain; Peritoneal; Peritoneal Fluid; Persistent pain; Phenotype; Plasma; Postoperative Pain; Prostaglandins; Quality of life; Regulation; Reporting; Research; Sampling; Symptoms; Time; Up-Regulation; Visualization; Woman; Women' s Health; base; biomarker discovery; cohort; comorbidity; diagnostic biomarker; diagnostic strategy; disorder risk; early detection biomarkers; endometriosis; experience; girls; hormone therapy; improved; metabolomics; molecular phenotype; novel; pain symptom; personalized medicine; predictive marker; social; treatment strategy; young adult; young woman; Adolescence; Adolescent; Adult; Affect; Arachidonic Acids; Biological; Biological Markers; Blood; CA-125 Antigen; Chronic Disease; Clinical; Color; Data; Diagnosis; Diagnostic; Disease; Dysmenorrhea; Early Diagnosis; Early Intervention; Economic Burden; Environment; Environmental Risk Factor; Functional disorder; Future; Genetic; Genome; Goals; Infertility; Lead; Lecithin; Lesion; Life Cycle Stages; Longitudinal cohort; Lysophosphatidylcholines; Machine Learning; Measurement; Measures; Metabolic Pathway; Molecular; Molecular Profiling; National Institute of Child Health and Human Development; Operative Surgical Procedures; Outcome; Pain; Pathway interactions; Patients; Pelvic Pain; Peritoneal; Peritoneal Fluid; Persistent pain; Phenotype; Plasma; Postoperative Pain; Prostaglandins; Quality of life; Regulation; Reporting; Research; Sampling; Symptoms; Time; Up-Regulation; Visualization; Woman; Women' s Health; base; biomarker discovery; cohort; comorbidity; diagnostic biomarker; diagnostic strategy; disorder risk; early detection biomarkers; endometriosis; experience; girls; hormone therapy; improved; metabolomics; molecular phenotype; novel; pain symptom; personalized medicine; predictive marker; social; treatment strategy; young adult; young woman

ABSTRACT Endometriosis is a debilitating disease affecting 200 million women worldwide, causing severe pain and infertility. Although over 50% of adults with endometriosis report onset of pain during adolescence, most women with endometriosis experience a delayed diagnosis on average of seven years due to the current diagnostic standard of surgical visualization, resulting in prolonged pain and decreased quality of life. Thus, there is a critical need to identify novel, non-invasive biomarkers for endometriosis, which is one of the NICHD research goals related to endometriosis. Being able to diagnose endometriosis earlier in the life course, during adolescence and young adulthood, may lead to earlier intervention and improved clinical outcome. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed in adolescents. Adolescent endometriosis typically presents with severe pelvic pain and superficial peritoneal lesions, which is distinct from adult-diagnosed endometriosis which typically present with pain, infertility, and deep fibrotic lesions. Furthermore, our preliminary data shows that about 30% of adolescents with endometriosis suffer from persistent or recurring post-surgical pelvic pain despite being treated with post-surgical hormone therapy, leading to recurring surgeries. Recently, we reported that blood CA125, which is elevated in endometriosis diagnosed in adults, was not elevated in adolescents with endometriosis. Adolescent-diagnosed endometriosis may have distinct molecular phenotype compared to adult-diagnosed endometriosis, which may require different strategies for diagnosis and treatment. The objective of this application is to identify novel (1) blood metabolomic profiles associated with adolescent endometriosis and (2) peritoneal fluid metabolomic markers predictive of persistent post-surgical pain. Metabolites are the downstream products of cellular activities regulated by the genome and modified by environmental factors and have proven valuable in biomarker discovery for many chronic diseases. Based on our preliminary data, upregulation of prostaglandin synthesis could be an important pathway for adolescent endometriosis pathophysiology given its common presentation with pain. Using the detailed clinical information, pain measures, plus paired blood and peritoneal fluid samples from the well-annotated longitudinal cohort of the Women’s Health Study: From Adolescence to Adulthood cohort, we will apply a validated metabolomics platform which can simultaneously measure over 600 metabolites, allowing us identify metabolites and biologic pathways unique to adolescent endometriosis. The proposed aims will identify novel metabolomic biomarkers of adolescent endometriosis which may lead to advances in determining early diagnostic biomarkers and personalized treatment strategies for endometriosis. Importantly, elucidating molecular profiles of adolescent endometriosis will provide new information about the pathophysiology during the earlier course the disease trajectory, informing future R01 proposals to elucidate changes in metabolomic profiles as the disease progresses from adolescence to adulthood.

抽象的 子宫内膜异位症是一种令人衰弱的疾病，影响了全世界的2亿女性，导致严重的疼痛和 不育。尽管有超过50％的子宫内膜异位症的成年人报告青少年疼痛发作，但大多数 子宫内膜异位症的妇女由于当前 手术可视化的诊断标准，导致疼痛延长和生活质量改善。那， 迫切需要识别新型的非侵入性生物标志物用于子宫内膜异位症，这是NICHD之一 与子宫内膜异位症有关的研究目标。能够在生命过程中早期诊断子宫内膜异位症 青少年和成年后，可能导致较早的干预和改善的临床结果。然而， 关于在青少年诊断的子宫内膜异位症的病理生理学和分子特征知之甚少。 青少年子宫内膜异位症通常表现出严重的骨盆疼痛和浅表腹膜病变，即 与成人诊断的子宫内膜异位症不同，通常表现出疼痛，不育和深纤维化 病变。此外，我们的初步数据表明，大约30％的子宫内膜异位症青少年患有 持续性或经常性的手术后骨盆疼痛被手术后的马内治疗治疗， 导致经常性手术。最近，我们报道了子宫内膜异位症升高的血液CA125 在成年人中被诊断出来，子宫内膜异位症的青少年没有升高。青少年诊断的子宫内膜异位症 与成人诊断的子宫内膜异位症相比，可能具有不同的分子表型，这可能需要 诊断和治疗的不同策略。该应用的目的是识别新颖的血液（1）血液 与青少年子宫内膜异位症和（2）腹膜液代谢组标记相关的代谢组谱 预测持续的手术后疼痛。代谢物是细胞活性的下游产物 由基因组调节，并由环境因素修改，并在生物标志物中得到证明价值 许多慢性疾病的发现。根据我们的初步数据，前列腺素合成的上调 鉴于其常见表现 痛苦。使用详细的临床信息，疼痛度量以及配对的血液和腹膜液样品 从妇女健康研究的纵向纵向队列：从青少年到成年 队列，我们​​将应用一个经过验证的代谢组学平台，该平台可以轻松测量600多个 代谢产物，使我们识别了青少年子宫内膜异位症独有的代谢物和生物学途径。这 拟议的目标将确定青少年子宫内膜异位症的新型代谢组生物标志物，这可能导致 确定早期诊断生物标志物和子宫内膜异位症个性化治疗策略的进步。 重要的是，阐明青少年子宫内膜异位症的分子谱将提供有关 疾病轨迹的早期病理生理学，告知未来R01的建议以阐明 随着疾病的发展，代谢组谱的变化从青春期发展到成年。