Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression. To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women’s Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012–2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. The median age at blood draw was 17 years (interquartile range, 15–19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal <.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44–6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28–5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36–0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04–14.33]). Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

中文翻译：

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患有子宫内膜异位症的青少年和年轻人的血浆蛋白和持续性盆腔疼痛

预测手术治疗反应的非侵入性生物标志物将为个性化治疗提供信息，并深入了解子宫内膜异位症相关疼痛和症状进展的潜在生物学途径。使用基于多重适体的蛋白质组学生物标志物发现平台，将血浆蛋白与主要患有子宫内膜异位症的青少年和年轻人腹腔镜手术后持续性盆腔疼痛相关。我们进行了一项前瞻性分析，纳入了《女性健康研究：从青春期到成年》观察性纵向队列中的 142 名经腹腔镜确诊患有子宫内膜异位症的参与者，研究入组时间为 2012 年至 2018 年。使用修改后的世界子宫内膜异位症研究基金会子宫内膜异位症表组和生物样本库协调项目工具收集生物样本和患者数据。在腹腔镜消融或切除子宫内膜异位症之前收集的血液中，我们使用 SomaScan 同时测量了 1305 个血浆蛋白水平，包括免疫、血管生成和炎症标记物。恶化或持续性术后盆腔疼痛定义为与术前相比，术后 1 年新出现、持续（即稳定）或恶化严重程度、频率或持续性生活干扰的痛经或非周期性盆腔疼痛。我们使用逻辑回归计算了比值比和 95% 置信区间，并根据年龄、体重指数、禁食状态和抽血时激素的使用进行了调整。我们应用 Ingenuity 通路分析和 STRING 分析来识别病理生理通路和蛋白质相互作用。抽血时的中位年龄为 17 岁（四分位数范围，15-19 岁），大多数参与者是白人 (90%)。所有患者均仅有浅表腹膜病变，并通过切除或消融进行治疗。术后一年，其中 76 名（54%）患有子宫内膜异位症的参与者盆腔疼痛恶化或持续，而 66 名（46%）参与者的盆腔疼痛有所改善。我们确定了 83 种与术后 1 年恶化或持续性骨盆疼痛相关的蛋白质（名义值 <.05）。与术后 1 年盆腔疼痛改善的患者相比，盆腔疼痛恶化或持续的患者血浆 CD63 抗原水平较高（比值比，2.98 [95% 置信区间，1.44–6.19]）和 CD47（比值比，2.68 [95% 置信区间，1.44-6.19]）。 95% 置信区间，1.28–5.61]），但术前血液中 Sonic Hedgehog 蛋白水平较低（比值比，0.55 [95% 置信区间，0.36–0.84]）。与疼痛改善的患者相比，术后盆腔疼痛恶化或持续的患者中，与细胞迁移相关的通路上调，与血管生成相关的通路下调。当我们检查从术前到术后蛋白质水平的变化及其随后在一年随访中恶化或持续性术后疼痛的风险时，我们观察到，从手术前到手术后，Sonic Hedgehog 蛋白水平不断增加，与术后疼痛风险增加 4 倍相关（比值比 [四分位数 4 vs 1]，3.86 [1.04–14.33]）。使用基于适体的蛋白质组学平台，我们确定了与青少年和年轻人子宫内膜异位症术后治疗恶化或持续盆腔疼痛相关的血浆蛋白和通路，这可能有助于对子宫内膜异位症患者进行风险分层。