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Harnessing biomarker and phenotypic diversity among adolescents and women with endometriosis to advance personalized medicine for diagnosis and pain remediation

利用患有子宫内膜异位症的青少年和女性的生物标志物和表型多样性来推进诊断和疼痛治疗的个性化医疗

基本信息

批准号：
9921458
负责人：
STACEY ANN MISSMER
金额：
$ 21.4万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-04-30
项目状态：
已结题

项目摘要

Project Summary/Abstract Endometriosis is a common disease among reproductive aged adolescents and women and can lead to debilitating pelvic pain, infertility, reduced quality of life and significant health care costs. Currently laparoscopic surgery is the only means for providing a definitive diagnosis of endometriosis. The average delay to diagnosis from symptom onset is 7 years, potentially leading to unchecked endometriotic lesion progression and increased risk and severity of morbidity later in adulthood. While numerous studies have investigated non- invasive screening tests for diagnosing endometriosis, none have proven to have sufficient specificity and/or sensitivity to replace laparoscopic surgery. Further, once an adolescent or woman has been diagnosed with endometriosis she often faces a struggle to find the most effective treatment modality to relieve endometriosis- related symptoms. While the revised American Society for Reproductive Medicine endometriosis staging and the Endometriosis Fertility Index have been used to predict prognosis after endometriosis diagnosis; neither is specific to predicting if adolescents and women will experience pain remediation. Additionally, a subset of endometriosis patients will develop central sensitization leading to treatment refractory chronic pelvic pain. The lack of discovery for a non-invasive screening test for endometriosis diagnosis and for monitoring disease progression may be due to considering endometriosis as a single entity and not including the full heterogeneity in symptom profiles and patient characteristics to assess diagnosis and pain remediation after treatment. Our proposal fills this scientific gap by (1) investigating a non-invasive diagnostic for endometriosis combining patient symptoms and characteristics with inflammatory, oxidative stress and central sensitization biomarkers; (2) assessing changes in inflammatory, oxidative stress and central sensitization biomarkers before and after surgery; and (3) determining the optimal set of patient symptoms and characteristics in addition to inflammatory, oxidative stress and central sensitization biomarkers to advance personalized treatment selection. We will assess inflammatory and oxidative stress biomarkers as an aberrant immune response and increased oxidative stress have been implicated in endometriosis etiology and progression. Collectively, these aims have the potential to advance our understanding of phenotypic diversity among adolescents and women with endometriosis; diversity that will be the foundation for successful personalized, precision medicine to shorten diagnostic delay and maximize pain remediation. Success will reduce health care costs and increase long-term health and quality of life for adolescents and women with endometriosis.

项目概要/摘要子宫内膜异位症是育龄青少年和妇女的常见疾病，可导致使人衰弱的盆腔疼痛、不孕、生活质量下降和高昂的医疗费用。目前腹腔镜手术是明确诊断子宫内膜异位症的唯一方法。平均诊断延迟从症状出现起 7 年，可能导致子宫内膜异位病变进展不受控制成年后期发病的风险和严重程度增加。虽然大量研究调查了非用于诊断子宫内膜异位症的侵入性筛查测试，尚未证明具有足够的特异性和/或敏感性取代腹腔镜手术。此外，一旦青少年或女性被诊断出患有子宫内膜异位症她经常面临寻找最有效的治疗方式来缓解子宫内膜异位症的斗争 - 相关症状。虽然修订后的美国生殖医学会子宫内膜异位症分期和子宫内膜异位症生育指数已用于预测子宫内膜异位症诊断后的预后；也不是具体用于预测青少年和女性是否会经历疼痛治疗。此外，一个子集子宫内膜异位症患者会产生中枢敏化，导致治疗难治性慢性盆腔疼痛。这缺乏用于子宫内膜异位症诊断和疾病监测的非侵入性筛查试验的发现进展可能是由于将子宫内膜异位症视为一个单一实体而不包括完整的异质性症状概况和患者特征，以评估治疗后的诊断和疼痛缓解。我们的该提案通过以下方式填补了这一科学空白：（1）研究子宫内膜异位症的非侵入性诊断，结合患者症状和炎症、氧化应激和中枢致敏生物标志物的特征； (2)评估治疗前后炎症、氧化应激和中枢致敏生物标志物的变化外科手术; (3) 确定一组最佳的患者症状和特征炎症、氧化应激和中枢敏化生物标志物以推进个性化治疗选择。我们将评估炎症和氧化应激生物标志物作为异常的免疫反应，氧化应激增加与子宫内膜异位症的病因和进展有关。总的来说，这些目标有可能增进我们对青少年和女性表型多样性的理解患有子宫内膜异位症；多样性将成为成功的个性化精准医疗的基础缩短诊断延迟并最大限度地缓解疼痛。成功将降低医疗保健成本并增加患有子宫内膜异位症的青少年和妇女的长期健康和生活质量。