Pospelova Maria, Krasnikova Varvara, Fionik Olga, Alekseeva Tatyana, Samochernykh Konstantin, Ivanova Nataliya, Trofimov Nikita, Vavilova Tatyana, Vasilieva Elena, Topuzova Maria, Chaykovskaya Alexandra, Makhanova Albina, Mikhalicheva Anna, Bukkieva Tatyana, Restor Kenneth, Combs Stephanie, Shevtsov Maxim
Personalized Medicine Centre, Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia.
Nursing Programme, University of St. Francis, Joliet, IL 60435, USA.
J Clin Med. 2022 Feb 24;11(5):1215. doi: 10.3390/jcm11051215.
Damage of the central nervous system (CNS), manifested by cognitive impairment, occurs in 80% of women with breast cancer (BC) as a complication of surgical treatment and radiochemotherapy. In this study, the levels of ICAM-1, PECAM-1, NSE, and anti-NR-2 antibodies which are associated with the damage of the CNS and the endothelium were measured in the blood by ELISA as potential biomarkers that might reflect pathogenetic mechanisms in these patients. A total of 102 patients enrolled in this single-center trial were divided into four groups: (1) 26 patients after breast cancer treatment, (2) 21 patients with chronic brain ischemia (CBI) and asymptomatic carotid stenosis (ICA stenosis) (CBI + ICA stenosis), (3) 35 patients with CBI but without asymptomatic carotid stenosis, and (4) 20 healthy female volunteers (control group). Intergroup analysis demonstrated that in the group of patients following BC treatment there was a significant increase of ICAM-1 (mean difference: −368.56, 95% CI −450.30 to −286.69, p < 0.001) and PECAM-1 (mean difference: −47.75, 95% CI −68.73 to −26.77, p < 0.001) molecules, as compared to the group of healthy volunteers. Additionally, a decrease of anti-NR-2 antibodies (mean difference: 0.89, 95% CI 0.41 to 1.48, p < 0.001) was detected. The intergroup comparison revealed comparable levels of ICAM-1 (mean difference: −33.58, 95% CI −58.10 to 125.26, p = 0.76), PECAM-1 (mean difference: −5.03, 95% CI −29.93 to 19.87, p = 0.95), as well as anti-NR-2 antibodies (mean difference: −0.05, 95% CI −0.26 to 0.16, p = 0.93) in patients after BC treatment and in patients with CBI + ICA stenosis. The NSE level in the group CBI + ICA stenosis was significantly higher than in women following BC treatment (mean difference: −43.64, 95% CI 3.31 to −83.99, p = 0.03). Comparable levels of ICAM-1 were also detected in patients after BC treatment and in the group of CBI (mean difference: −21.28, 95% CI −111.03 to 68.48, p = 0.92). The level of PECAM-1 molecules in patients after BC treatment was also comparable to group of CBI (mean difference: −13.68, 95% CI −35.51 to 8.15, p = 0.35). In conclusion, among other mechanisms, endothelial dysfunction might play a role in the damage of the CNS in breast cancer survivors.
中枢神经系统（CNS）损伤表现为认知障碍，在80%的乳腺癌（BC）女性患者中作为手术治疗和放化疗的并发症出现。在本研究中，通过酶联免疫吸附测定法（ELISA）检测血液中与中枢神经系统和内皮损伤相关的细胞间黏附分子-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）和抗NR-2抗体的水平，作为可能反映这些患者发病机制的潜在生物标志物。共有102名参与这项单中心试验的患者被分为四组：（1）26名乳腺癌治疗后的患者；（2）21名患有慢性脑缺血（CBI）和无症状颈动脉狭窄（ICA狭窄）（CBI + ICA狭窄）的患者；（3）35名患有CBI但无无症状颈动脉狭窄的患者；（4）20名健康女性志愿者（对照组）。组间分析表明，与健康志愿者组相比，乳腺癌治疗后的患者组中ICAM-1（平均差异：-368.56，95%置信区间-450.30至-286.69，p < 0.001）和PECAM-1（平均差异：-47.75，95%置信区间-68.73至-26.77，p < 0.001）分子显著增加。此外，检测到抗NR-2抗体减少（平均差异：0.89，95%置信区间0.41至1.48，p < 0.001）。组间比较显示，乳腺癌治疗后的患者和CBI + ICA狭窄患者中ICAM-1（平均差异：-33.58，95%置信区间-58.10至125.26，p = 0.76）、PECAM-1（平均差异：-5.03，95%置信区间-29.93至19.87，p = 0.95）以及抗NR-2抗体（平均差异：-0.05，95%置信区间-0.26至0.16，p = 0.93）水平相当。CBI + ICA狭窄组中的NSE水平显著高于乳腺癌治疗后的女性患者（平均差异：-43.64，95%置信区间3.31至-83.99，p = 0.03）。在乳腺癌治疗后的患者和CBI组中也检测到相当的ICAM-1水平（平均差异：-21.28，95%置信区间-111.03至68.48，p = 0.92）。乳腺癌治疗后的患者中PECAM-1分子水平也与CBI组相当（平均差异：-13.68，95%置信区间-35.51至8.15，p = 0.35）。总之，在内皮功能障碍等其他机制中，其可能在乳腺癌幸存者的中枢神经系统损伤中起作用。
