Proteomic Analysis of Serum Samples in Ovulatory Polycystic Ovary Syndrome and Construction of a Protein Interaction Pathway.

IF 1.4
Ahmad Fazilat, Keivan Majidzadeh-A, Kambiz Gilany, Fatemeh Mortazavi Moghadam, Mohammad Valilo, Saima Wajid
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Abstract

As a heterogeneous multifactorial disorder, PCOS still has a misty etiology. Its underlying pathophysiological causes can be further elucidated by proteomic analyses and molecular network analysis to understand the interaction pathways involved in the PCOS-associated perturbations. We conducted a proteomic study on ovulatory PCOS serum samples using nano-LCMS/MS technique. Then, we analysed the proteomic profiles of substantially dysregulated proteins by projecting them onto protein interaction mapping and molecular network analysis software tools Gene Mania and STRING. We further investigated the involvement of the affected proteins in different PCOS-associated disorders and classified them through a review of the literature along with functional annotation software tools DAVID and Panther. We found a total of 228 proteins in serum; 109 were found in both ovulatory PCOS and controls, and 42 of those showed a difference of ≥twofold (19 higher in ovulatory PCOS and 23 lower). Among them, 35 proteins exhibited an association with the pathophysiological mechanisms underlying the manifestation of ovulatory PCOS manifestation and their correlations with PCOS-concurrent disorders were revealed. There were also 87 proteins that were only found in ovulatory PCOS and 32 that were only found in controls. We further highlighted significant functional hub molecules within protein interaction networks. Our findings indicated that the ovulatory PCOS involves a wide range of functional molecule derangements, which trigger aberrant biological responses and molecular interactions leading to the emergence of complications associated with ovulatory PCOS. Further omics studies are required to explain the different physiological mechanisms of the functional molecules contributing to the pathogenicity of this heterogeneous syndrome.

排卵期多囊卵巢综合征血清蛋白组学分析及蛋白相互作用途径的构建。
多囊卵巢综合征是一种异质性多因素疾病,病因不明。其潜在的病理生理原因可以通过蛋白质组学分析和分子网络分析进一步阐明,以了解pcos相关扰动所涉及的相互作用途径。采用纳米lcms /MS技术对PCOS排卵期血清样本进行蛋白质组学研究。然后,我们通过将其投射到蛋白质相互作用图谱和分子网络分析软件工具Gene Mania和STRING上,分析了严重失调蛋白的蛋白质组学特征。我们进一步研究了不同pcos相关疾病中受影响蛋白的参与,并通过文献综述以及功能注释软件工具DAVID和Panther对它们进行了分类。我们在血清中发现了228种蛋白质;排卵期PCOS与对照组均有109例,其中42例差异≥2倍(排卵期PCOS高19例,低23例)。其中,35种蛋白与排卵期PCOS表现的病理生理机制相关,并与PCOS并发疾病相关。还有87种蛋白质仅在排卵期多囊卵巢综合征中发现,32种仅在对照组中发现。我们进一步强调了蛋白质相互作用网络中重要的功能枢纽分子。我们的研究结果表明,排卵期PCOS涉及广泛的功能分子紊乱,引发异常的生物学反应和分子相互作用,导致排卵期PCOS相关并发症的出现。需要进一步的组学研究来解释导致这种异质性综合征致病性的功能分子的不同生理机制。
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