Plasma proteomic profiles of pain subtypes in adolescents and young adults with endometriosis.
Plasma proteomic profiles of pain subtypes in adolescents and young adults with endometriosis.
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DOI：
10.1093/humrep/dead099
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发表时间：
2023-05
影响因子：
6.1
通讯作者：
Naoko Sasamoto;L. Ngo;A. Vitonis;S. Dillon;C. Sieberg;S. Missmer;T. Libermann;K. Terry
中科院分区：
文献类型：
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作者：
Naoko Sasamoto;L. Ngo;A. Vitonis;S. Dillon;C. Sieberg;S. Missmer;T. Libermann;K. Terry
研究问题：在患有子宫内膜异位症的青少年和年轻人中，子宫内膜异位症相关疼痛亚型的系统蛋白质组学特征有什么相似和不同之处？子宫内膜异位症相关疼痛亚型表现出不同的血浆蛋白质组学特征。已知的是，子宫内膜异位症患者，特别是那些被诊断为青少年和年轻人的患者，经常受到各种疼痛症状的困扰。然而，目前还不清楚是什么生物过程导致了这种异质性。研究设计、规模、持续时间我们利用142名参加妇女健康研究的青春期或青壮年参与者的数据和血浆样本进行了横断面分析：从青春期到成年期，经腹腔镜确诊的子宫内膜异位症患者。对象/材料、环境、方法用SomaScan测定1305例血浆蛋白水平。我们将自己报告的子宫内膜异位症相关疼痛分为痛经、非周期性盆腔疼痛、影响生活的盆腔疼痛、膀胱痛、肠痛和广泛性疼痛的亚型。我们使用Logistic回归来计算差异表达蛋白的优势比和95%的可信区间，调整了年龄、BMI、空腹状态和抽血时激素的使用。独创性路径分析确定了丰富的生物路径。主要结果和偶然性的作用我们的研究人群主要是青少年和青壮年(平均抽血年龄=18岁)，几乎所有(97%)在腹腔镜下诊断为子宫内膜异位症的患者(97%)都被评为rASRM I/II期，这是子宫内膜异位症较年轻诊断的常见临床表现。疼痛亚型表现出不同的血浆蛋白质组学特征。在有严重痛经和影响生活的盆腔疼痛患者中，多个细胞运动通路的表达较无痛经患者下调(P<；7.5×10-15)。子宫内膜异位症伴非循环性盆腔疼痛患者免疫细胞黏附途径上调(P<；9.0×10-9)，膀胱痛患者免疫细胞迁移上调(P<；3.7×10-8)，肠痛患者免疫细胞迁移途径下调(P<；6.5×10-7)。广泛的疼痛表型涉及多种免疫途径的下调(P<；8.0×10-10)。限制，谨慎的理由我们的研究因缺乏独立的验证队列而受到限制。我们也只能探索疼痛亚型的任何存在，而不能根据疼痛亚型评估多种组合。有必要进行进一步的机制研究，以阐明子宫内膜异位症疼痛亚型在病理生理学上的差异。研究结果的更广泛意义观察到不同疼痛亚型的血浆蛋白谱差异表明了不同的潜在分子机制，突出了考虑疼痛亚型的潜在需要，以有效地治疗出现各种疼痛症状的子宫内膜异位症患者。研究资助/竞争利益(S)本研究得到了国防部W81XWH1910318和2017年波士顿子宫内膜异位症中心学员奖的支持。J·威拉德和爱丽丝·S·万豪基金会为A2A队列的建立和数据收集提供了财政支持。N.S.、A.F.V.、S.A.M.和K.L.T.都得到了万豪家庭基金会的资助。CBS由NIGMS(5R35GM142676)颁发的R35 Mira奖资助。S.A.M.和K.L.T.由NICHD R01HD094842支持。S.A.M.报告说，作为AbbVie和Roche的顾问委员会成员，AbbVie和Roche是生殖健康前沿的现场主编，雅培公司支付参加圆桌会议的个人费用；这些都与本研究无关。其他作者报告说没有利益冲突。试用注册号N/A
STUDY QUESTION What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis? SUMMARY ANSWER Endometriosis-associated pain subtypes exhibited distinct plasma proteomic profiles. WHAT IS KNOWN ALREADY Endometriosis patients, especially those diagnosed in adolescents and young adults, are often plagued by various pain symptoms. However, it is not clear what biological processes underlie this heterogeneity. STUDY DESIGN, SIZE, DURATION We conducted a cross-sectional analysis using data and plasma samples from 142 adolescent or young adult participants of the Women's Health Study: From Adolescence to Adulthood cohort with laparoscopically confirmed endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS We measured 1305 plasma protein levels by SomaScan. We classified self-reported endometriosis-associated pain into subtypes of dysmenorrhea, acyclic pelvic pain, life impacting pelvic pain, bladder pain, bowel pain, and widespread pain phenotype. We used logistic regression to calculate the odds ratios and 95% confidence intervals for differentially expressed proteins, adjusting for age, BMI, fasting status, and hormone use at blood draw. Ingenuity Pathway Analysis identified enriched biological pathways. MAIN RESULTS AND THE ROLE OF CHANCE Our study population consisted mainly of adolescents and young adults (mean age at blood draw = 18 years), with nearly all (97%) scored as rASRM stage I/II at laparoscopic diagnosis of endometriosis, which is a common clinical presentation of endometriosis diagnosed at a younger age. Pain subtypes exhibited distinct plasma proteomic profiles. Multiple cell movement pathways were downregulated in cases with severe dysmenorrhea and life impacting pelvic pain compared to those without (P < 7.5×10-15). Endometriosis cases with acyclic pelvic pain had upregulation of immune cell adhesion pathways (P < 9.0×10-9), while those with bladder pain had upregulation of immune cell migration (P < 3.7×10-8) and those with bowel pain had downregulation (P < 6.5×10-7) of the immune cell migration pathways compared to those without. Having a wide-spread pain phenotype involved downregulation of multiple immune pathways (P < 8.0×10-10). LIMITATIONS, REASONS FOR CAUTION Our study was limited by the lack of an independent validation cohort. We were also only able to explore any presence of a pain subtype and could not evaluate multiple combinations by pain subtypes. Further mechanistic studies are warranted to elucidate the differences in pathophysiology by endometriosis-pain subtype. WIDER IMPLICATIONS OF THE FINDINGS The observed variation in plasma protein profiles by pain subtypes suggests different underlying molecular mechanisms, highlighting the need for potential consideration of pain subtypes for effectively treating endometriosis patients presenting with various pain symptoms. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Department of Defense W81XWH1910318 and the 2017 Boston Center for Endometriosis Trainee Award. Financial support for establishment of and data collection within the A2A cohort were provided by the J. Willard and Alice S. Marriott Foundation. N.S., A.F.V., S.A.M., and K.L.T. have received funding from the Marriott Family Foundation. C.B.S. is funded by an R35 MIRA Award from NIGMS (5R35GM142676). S.A.M. and K.L.T. are supported by NICHD R01HD094842. S.A.M. reports serving as an advisory board member for AbbVie and Roche, Field Chief Editor for Frontiers in Reproductive Health, personal fees from Abbott for roundtable participation; none of these are related to this study. Other authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.