Starodubtseva Natalia L, Tokareva Alisa O, Rodionov Valeriy V, Brzhozovskiy Alexander G, Bugrova Anna E, Chagovets Vitaliy V, Kometova Vlada V, Kukaev Evgenii N, Soares Nelson C, Kovalev Grigoriy I, Kononikhin Alexey S, Frankevich Vladimir E, Nikolaev Evgeny N, Sukhikh Gennady T
V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, 117997 Moscow, Russia.
Department of Chemical Physics, Moscow Institute of Physics and Technology, 141700 Moscow, Russia.
Biomedicines. 2023 Jun 22;11(7):1786. doi: 10.3390/biomedicines11071786.
Metastasis is a serious and often life-threatening condition, representing the leading cause of death among women with breast cancer (BC). Although the current clinical classification of BC is well-established, the addition of minimally invasive laboratory tests based on peripheral blood biomarkers that reflect pathological changes in the body is of utmost importance. In the current study, the serum proteome and lipidome profiles for 50 BC patients with (25) and without (25) metastasis were studied. Targeted proteomic analysis for concertation measurements of 125 proteins in the serum was performed via liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) using the BAK 125 kit (MRM Proteomics Inc., Victoria, BC, Canada). Untargeted label-free lipidomic analysis was performed using liquid chromatography coupled to tandem mass-spectrometry (LC-MS/MS), in both positive and negative ion modes. Finally, 87 serum proteins and 295 lipids were quantified and showed a moderate correlation with tumor grade, histological and biological subtypes, and the number of lymph node metastases. Two highly accurate classifiers that enabled distinguishing between metastatic and non-metastatic BC were developed based on proteomic (accuracy 90%) and lipidomic (accuracy 80%) features. The best classifier (91% sensitivity, 89% specificity, AUC = 0.92) for BC metastasis diagnostics was based on logistic regression and the serum levels of 11 proteins: alpha-2-macroglobulin, coagulation factor XII, adiponectin, leucine-rich alpha-2-glycoprotein, alpha-2-HS-glycoprotein, Ig mu chain C region, apolipoprotein C-IV, carbonic anhydrase 1, apolipoprotein A-II, apolipoprotein C-II and alpha-1-acid glycoprotein 1.
转移是一种严重且常常危及生命的状况，是乳腺癌（BC）女性患者的主要死因。尽管目前BC的临床分类已很成熟，但基于反映身体病理变化的外周血生物标志物添加微创实验室检测至关重要。在本研究中，对50例有转移（25例）和无转移（25例）的BC患者的血清蛋白质组和脂质组谱进行了研究。使用BAK 125试剂盒（MRM Proteomics Inc.，加拿大不列颠哥伦比亚省维多利亚市），通过液相色谱 - 多反应监测质谱（LC - MRM MS）对血清中125种蛋白质进行靶向蛋白质组分析以进行浓度测量。使用液相色谱与串联质谱联用（LC - MS/MS），在正离子和负离子模式下进行非靶向无标记脂质组分析。最后，对87种血清蛋白和295种脂质进行了定量，结果显示它们与肿瘤分级、组织学和生物学亚型以及淋巴结转移数量呈中度相关。基于蛋白质组学（准确率90%）和脂质组学（准确率80%）特征开发了两种能够区分转移性和非转移性BC的高度准确的分类器。用于BC转移诊断的最佳分类器（灵敏度91%，特异性89%，AUC = 0.92）基于逻辑回归和11种蛋白质的血清水平：α-2-巨球蛋白、凝血因子XII、脂联素、富含亮氨酸的α-2-糖蛋白、α-2-HS-糖蛋白、Igμ链C区、载脂蛋白C-IV、碳酸酐酶1、载脂蛋白A-II、载脂蛋白C-II和α-1-酸性糖蛋白1。
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