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蛋白质组学分析腹膜液发现 COMP 和 TGFBI 是子宫内膜异位症的新候选生物标志物。

Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis.

机构信息

Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Šlajmerjeva 3, 1000, Ljubljana, Slovenia.

Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.

出版信息

Sci Rep. 2021 Oct 22;11(1):20870. doi: 10.1038/s41598-021-00299-2.

Abstract

Endometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case-control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in cases versus the control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of > 0.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.

摘要

子宫内膜异位症是一种常见的非恶性妇科疾病,严重影响大多数患者的生育能力和生活质量。诊断的金标准是通过手术腹腔镜检查盆腔器官,目前还没有可以进行非侵入性诊断的生物标志物。子宫内膜异位症的发病机制尚不完全清楚,因此对腹腔液的分析可能对此有所帮助。我们的前瞻性病例对照研究包括 58 名因不孕接受腹腔镜检查的患者,其中 32 名患有腹膜子宫内膜异位症(病例),26 名患有不明原因的原发性不孕(对照组)。使用覆盖 1360 种蛋白质的抗体微阵列进行发现蛋白质组学分析,鉴定出 16 种在病例与对照组患者之间水平不同的蛋白质。使用 ELISA 方法进行验证,证实软骨寡聚基质蛋白(COMP)和转化生长因子-β诱导蛋白 ig-h3(TGFBI)的水平存在显著差异,血管紧张素原(AGT)的水平没有差异。基于线性支持向量机的分类模型显示 AUC >0.83,灵敏度为 0.81,特异性为 1.00。差异表达的蛋白质代表诊断和预后生物标志物或药物靶点的候选物。我们的研究结果带来了新的知识,有助于理解子宫内膜异位症的病理生理学,并需要进一步在血液样本中进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7d8/8536751/41fec630e803/41598_2021_299_Fig1_HTML.jpg

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