Kopeć Jakub, Sałacińska-Łoś Elżbieta, Orzechowska Magdalena, Sokolnicka Monika, Gawłowska-Marciniak Aleksandra, Przemysław Przewratil
Pediatric Surgery and Oncology Department, Medical University of Łódź, 90-419 Lodz, Poland.
Molecular Carcinogenesis Department, Medical University of Łódź, 90-752 Lodz, Poland.
Diagnostics (Basel). 2023 Dec 25;14(1):38. doi: 10.3390/diagnostics14010038.
Vascular anomalies often result in aesthetic flaws, pain, and impair the quality of life. They require challenging treatments that frequently do not provide the desired results. The mammalian target of rapamycin (mTOR) is directly involved in the development of these malformations. However, the exact mechanism behind mTOR dysregulation has not been unambiguously defined. The purpose of this study is to investigate the activation of selected substrates of mTOR to partially assess its involvement in the disease process.
We analyzed tissue samples collected from patients with vascular anomalies treated in our department. We included patients with histopathological diagnoses of lymphatic, venous, capillary malformations, mixed lesions, and a control group of healthy skin samples. We stained the samples using H and E and immunohistochemistry. We used primary antibodies against p70 S6 Kinase, 4EBP1, and p-4EBP1. We graded their color reactions. The statistical analyses were performed using the FactoMineR and factoextra R v.4.1 packages. -values < 0.05 were considered statistically significant.
The analysis of 82 patients showed that healthy tissue vessels expressed lower levels of tested mTOR pathway substrates compared to high activation in vascular malformations. Elevated substrate expression in a comparison between sexes revealed higher P-4EBP1 expression in the female malformation group. We observed a decrease in mTOR substrate expression with age.
The higher expression of mTOR substrates in vascular malformations compared to healthy tissue confirms their involvement in abnormal vascular development. Age-related changes in mTOR substrate expression highlight the need for timely intervention. Our study contributes to the understanding of the mTOR signaling pathway in vascular malformations and highlights its potential as a therapeutic target, contributing to personalized medicine.
血管异常常导致美学缺陷、疼痛，并损害生活质量。它们需要具有挑战性的治疗方法，但这些治疗常常无法达到预期效果。雷帕霉素靶蛋白（mTOR）直接参与这些畸形的发展。然而，mTOR失调背后的确切机制尚未明确界定。本研究的目的是研究mTOR选定底物的激活情况，以部分评估其在疾病过程中的作用。
我们分析了从我院接受治疗的血管异常患者身上采集的组织样本。我们纳入了经组织病理学诊断为淋巴管畸形、静脉畸形、毛细血管畸形、混合性病变的患者，以及一组健康皮肤样本作为对照组。我们使用苏木精和伊红染色以及免疫组织化学对样本进行染色。我们使用了针对p70 S6激酶、4EBP1和磷酸化4EBP1的一抗。我们对它们的颜色反应进行分级。使用FactoMineR和factoextra R v.4.1软件包进行统计分析。P值<0.05被认为具有统计学意义。
对82例患者的分析表明，与血管畸形中高激活水平相比，健康组织血管中检测的mTOR通路底物表达水平较低。在性别比较中底物表达升高，显示女性畸形组中磷酸化4EBP1表达较高。我们观察到mTOR底物表达随年龄下降。
与健康组织相比，血管畸形中mTOR底物的较高表达证实了它们参与异常血管发育。mTOR底物表达的年龄相关变化突出了及时干预的必要性。我们的研究有助于理解血管畸形中的mTOR信号通路，并突出其作为治疗靶点的潜力，为个性化医疗做出贡献。
