背景:在妇科恶性肿瘤中,子宫内膜癌(EC)是影响女性的最常见的子宫癌类型。这项研究探索了从EC患者获得的血浆样品的蛋白质组学图谱,那些有增生(Hy),和对照组(CO)。技术的组合,例如2D-DIGE,质谱,和生物信息学,包括途径分析,用于鉴定表达水平改变的蛋白质,这些组中的生物标志物及其相关的代谢途径。
方法:34名患者,分为三组-10与EC,12和Hy,研究中纳入了年龄在46至75岁之间的12名CO。使用凝胶电泳中的二维差异(2D-DIGE)与基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)进行非靶向蛋白质组学分析。
结果:在所有三组中,使用肽质量指纹(PMF)成功鉴定了114种显著(p≤0.05和倍数变化≥1.5)改变的蛋白质。与对照组(CO)相比,EC样品有85种差异表达的蛋白质(39种上调,46种下调),在Hy组中,与CO组相比,有81种蛋白质失调(40种上调,41种下调),与Hy组相比,EC血浆样品中33种蛋白质表现出差异调节(12种上调,21种下调)。维生素D结合蛋白和补体C3将Hy和EC与CO区分开,表达变化最大。在鉴定的差异表达蛋白质中,具有催化活性的酶占最大组(42.9%)。就生物过程而言,大多数蛋白质参与细胞过程(28.8%),其次是代谢过程(16.7%)。蛋白质相互作用的STRING分析显示,三组中显著差异丰富的蛋白质参与三个主要的生物学过程:补体和凝血级联的信号传导,通过胰岛素样生长因子结合蛋白(IGFBPs)调节胰岛素样生长因子(IGF)的转运和摄取,和血浆脂蛋白组装,重塑,和间隙。
结论:已鉴定的血浆蛋白标志物具有作为区分EC和Hy的生物标志物的潜力,以及癌症进展的早期诊断和监测。
BACKGROUND: Among gynaecological malignancies, endometrial cancer (EC) is the most prevalent type of uterine cancer affecting women. This study explored the proteomic profiles of plasma samples obtained from EC patients, those with hyperplasia (Hy), and a control group (CO). A combination of techniques, such as 2D-DIGE, mass spectrometry, and bioinformatics, including pathway analysis, was used to identify proteins with modified expression levels, biomarkers and their associated metabolic pathways in these groups.
METHODS: Thirty-four patients, categorized into three groups-10 with EC, 12 with Hy, and 12 CO-between the ages of 46 and 75 years old were included in the study. Untargeted proteomic analysis was carried out using two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
RESULTS: In all three groups, 114 proteins that were significantly (p ≤ 0.05 and fold change ≥ 1.5) altered were successfully identified using peptide mass fingerprints (PMFs). Compared with those in the control group (CO), the EC samples had 85 differentially expressed proteins (39 upregulated and 46 downregulated), and in the Hy group, 81 proteins were dysregulated (40 upregulated and 41 downregulated) compared to those in the CO group, while 33 proteins exhibited differential regulation (12 upregulated and 21 downregulated) in the EC plasma samples compared to those in the Hy group. Vitamin D binding protein and complement C3 distinguished Hy and EC from CO with the greatest changes in expression. Among the differentially expressed proteins identified, enzymes with catalytic activity represented the largest group (42.9%). In terms of biological processes, most of the proteins were involved in cellular processes (28.8%), followed by metabolic processes (16.7%). STRING analysis for protein interactions revealed that the significantly differentially abundant proteins in the three groups are involved in three main biological processes: signalling of complement and coagulation cascades, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), and plasma lipoprotein assembly, remodelling, and clearance.
CONCLUSIONS: The identified plasma protein markers have the potential to serve as biomarkers for differentiating between EC and Hy, as well as for early diagnosis and monitoring of cancer progression.