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血清蛋白质组学分析重度抑郁症患者及其缓解状态:锌-α-2-糖蛋白和角蛋白Ⅱ细胞骨架 1 的新型生物标志物集。

Serum proteomic analysis of major depressive disorder patients and their remission status: Novel biomarker set of zinc-alpha-2-glycoprotein and keratin type II cytoskeletal 1.

机构信息

Department of Senior Healthcare, Graduate School, Eulji University, Seongnam 13135, Republic of Korea.

Department of Neuropsychiatry, School of Medicine, Eulji University, Daejeon, Republic of Korea; Department of Psychiatry, Uijeongbu Eulji Medical Center, Eulji University, Gyeonggi, Republic of Korea.

出版信息

Int J Biol Macromol. 2021 Jul 31;183:2001-2008. doi: 10.1016/j.ijbiomac.2021.05.172. Epub 2021 May 27.

DOI:10.1016/j.ijbiomac.2021.05.172
PMID:34052271
Abstract

Major depressive disorder (MDD) is the most common mood disorder, and causes various mental, physical and cognitive symptoms. Clinicians diagnose MDD using multiple interviews and overall impression during the interviews, which makes MDD diagnosis highly subjective. To overcome this, we investigated novel protein biomarker for MDD. Serum from each subject were analyzed using nano liquid chromatography-triple time-of-flight mass spectrometry. We identified two proteins, zinc-alpha-2-glycoprotein (ZA2G) and keratin type II cytoskeletal 1 (K2C1), as final biomarkers. These biomarkers were downregulated during depression (p < 0.05, AUC of ROC >0.7). ZA2G is related to tryptophan metabolism, which is a main serotonin synthesis pathway. K2C1 is involved in the kinin-kallikrein system, which produces bradykinin, an anti-inflammatory mediator in the brain. Our results suggest that the two protein candidates are related to inflammation and that MDD is highly associated with inflammation. Finally, since all subjects in the two groups were taking antidepressants, our results suggest that the identified biomarkers could determine the presence or absence of illness and could be used to monitor therapeutic effects.

摘要

重度抑郁症(MDD)是最常见的情绪障碍,会引起各种精神、身体和认知症状。临床医生通过多次访谈和访谈中的整体印象来诊断 MDD,这使得 MDD 的诊断非常主观。为了克服这一问题,我们研究了 MDD 的新型蛋白质生物标志物。使用纳升液相色谱-三重飞行时间质谱对每位受试者的血清进行分析。我们确定了两种蛋白质,锌-α-2-糖蛋白(ZA2G)和角蛋白类型 II 细胞骨架 1(K2C1)作为最终的生物标志物。这些生物标志物在抑郁症期间下调(p < 0.05,ROC 的 AUC > 0.7)。ZA2G 与色氨酸代谢有关,色氨酸代谢是 5-羟色胺合成的主要途径。K2C1 参与激肽-激肽释放酶系统,该系统产生缓激肽,是大脑中的一种抗炎介质。我们的结果表明,这两种候选蛋白与炎症有关,而 MDD 与炎症高度相关。最后,由于两组中的所有受试者都在服用抗抑郁药,我们的结果表明,所鉴定的生物标志物可以确定疾病的存在与否,并可用于监测治疗效果。

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