Metabolomic profiling of adolescent endometriosis

青少年子宫内膜异位症的代谢组学分析

基本信息

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
项目类别：
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&apos 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

项目摘要

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使人衰弱的疾病，影响着全世界 2 亿女性，导致剧烈疼痛和尽管超过 50% 的子宫内膜异位症成人报告在青春期出现疼痛，但大多数由于目前的现状，患有子宫内膜异位症的女性平均诊断延迟七年手术可视化诊断标准，导致疼痛延长，生活质量下降。迫切需要确定子宫内膜异位症的新型非侵入性生物标志物，子宫内膜异位症是 NICHD 的研究之一与子宫内膜异位症相关的研究目标能够在生命过程的早期诊断子宫内膜异位症。青春期和成年早期，可能会导致早期干预并改善临床结果。关于青少年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为严重的盆腔疼痛和浅表腹膜病变，与成人诊断的子宫内膜异位症不同，后者通常表现为疼痛、不孕和深度纤维化此外，我们的初步数据显示，大约 30% 的青少年患有子宫内膜异位症。尽管接受术后激素治疗，但术后盆腔疼痛持续或反复出现，最近，我们报道了子宫内膜异位症患者血液 CA125 升高。在成人中诊断的子宫内膜异位症患者中，该值并未升高。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，这可能需要该应用程序的目的是识别新的 (1) 血液。与青少年子宫内膜异位症相关的代谢组学特征和 (2) 腹膜液代谢组学标志物代谢物是细胞活动的下游产物。受基因组调节并受环境因素修饰，并已被证明在生物标志物中有价值根据我们的初步数据，发现前列腺素合成上调。鉴于其常见表现，可能是青少年子宫内膜异位症病理生理学的重要途径使用详细的临床信息、疼痛测量以及配对的血液和腹膜液样本。来自女性健康研究的详细注释纵向队列：从青春期到成年队列中，我们将应用经过验证的代谢组学平台，该平台可以同时测量 600 多个代谢物，使我们能够识别青少年子宫内膜异位症特有的代谢物和生物途径。拟议的目标将确定青少年子宫内膜异位症的新代谢组生物标志物，这可能导致确定子宫内膜异位症早期诊断生物标志物和个性化治疗策略的进展。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青春期子宫内膜异位症的新信息。疾病轨迹早期病程的病理生理学，为未来的 R01 建议阐明提供信息随着疾病从青春期发展到成年，代谢组学特征发生变化。