Nikolaeva Alexandra, Pospelova Maria, Krasnikova Varvara, Makhanova Albina, Tonyan Samvel, Krasnopeev Yurii, Kayumova Evgeniya, Vasilieva Elena, Efimtsev Aleksandr, Levchuk Anatoliy, Trufanov Gennadiy, Voynov Mark, Shevtsov Maxim
Personalized Medicine Centre, Almazov National Medical Research Centre, Akkuratova Str. 2, 197341 Saint Petersburg, Russia.
Department of Radiation Oncology, Technishe Universität München (TUM), Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany.
Pathophysiology. 2023 Jun 15;30(2):260-274. doi: 10.3390/pathophysiology30020022.
Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients' quality of life. The identification of novel potential biomarkers that might help to predict the onset of VAS and its progression could improve the management of this group of patients. In the current study, the levels of intercellular cell adhesion molecule 1 (ICAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), NSE (neuron-specific enolase), and the antibodies recognizing NR-2 subunit of NMDA receptor (NR-2-ab) were measured in the blood serum of BC survivor patients with vestibulo-atactic syndrome (VAS) and associated with the brain connectome data obtained via functional magnetic resonance imaging (fMRI) studies. A total of 21 patients were registered in this open, single-center trial and compared to age-matched healthy female volunteers (control group) ( = 17). BC patients with VAS demonstrated higher serum levels of ICAM-1, PECAM-1, and NSE and a lower value of NR-2-ab, with values of 654.7 ± 184.8, 115.3 ± 37.03, 49.9 ± 103.9, and 0.5 ± 0.3 pg/mL, respectively, as compared to the healthy volunteers, with 230.2 ± 44.8, 62.8 ± 15.6, 15.5 ± 6.4, and 1.4 ± 0.7 pg/mL. According to the fMRI data (employing seed-to-voxel and ROI-to-ROI methods), in BC patients with VAS, significant changes were detected in the functional connectivity in the areas involved in the regulation of postural-tonic reflexes, the coordination of movements, and the regulation of balance. In conclusion, the detected elevated levels of serum biomarkers may reveal damage to the CNS neurons and endothelial cells that is, in turn, associated with the change in the brain connectivity in this group of patients.
前庭共济失调综合征（VAS）是运动和前庭障碍的一种组合，可表现为乳腺癌治疗的临床并发症，对患者的生活质量有重大影响。识别可能有助于预测VAS发病及其进展的新型潜在生物标志物，可改善对这组患者的管理。在当前研究中，测量了患有前庭共济失调综合征（VAS）的乳腺癌幸存者患者血清中的细胞间黏附分子1（ICAM - 1）、血小板/内皮细胞黏附分子1（PECAM - 1）、神经元特异性烯醇化酶（NSE）以及识别N - 甲基 - D - 天冬氨酸受体NR - 2亚基的抗体（NR - 2 - ab）水平，并将其与通过功能磁共振成像（fMRI）研究获得的脑连接组数据相关联。共有21名患者登记参加了这项开放的单中心试验，并与年龄匹配的健康女性志愿者（对照组）（n = 17）进行比较。患有VAS的乳腺癌患者血清中ICAM - 1、PECAM - 1和NSE水平较高，而NR - 2 - ab值较低，与健康志愿者相比，其值分别为654.7±184.8、115.3±37.03、49.9±103.9和0.5±0.3 pg/mL，而健康志愿者的值分别为230.2±44.8、62.8±15.6、15.5±6.4和1.4±0.7 pg/mL。根据fMRI数据（采用种子点到体素和感兴趣区域到感兴趣区域的方法），在患有VAS的乳腺癌患者中，在参与姿势紧张反射调节、运动协调和平衡调节的区域的功能连接中检测到显著变化。总之，检测到的血清生物标志物水平升高可能揭示中枢神经系统神经元和内皮细胞的损伤，而这又与该组患者脑连接性的变化相关。
