综合性转录和机器学习分析揭示了MRONJ中的免疫-炎症和压力反应变化
Galina Laputková1, Ivan Talian1, Ján Sabo1
1Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University, 040 11 Košice, Slovakia.
International journal of molecular sciences
|December 30, 2025
概括
与药物相关的下骨硬化 (MRONJ) 涉及基因表达的改变,特别是在核糖体和免疫通路中. 这项研究确定了可以帮助诊断和评估MRONJ.风险的关键基因.
科学领域:
- 基因组学和分子生物学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 与药物相关的骨 (MRONJ) 是抗吸收和抗血管治疗的严重并发症.
- 目前尚不清楚MRONJ背后的精确分子机制.
研究的目的:
- 通过分析基因表达特征来研究MRONJ的分子机制.
- 为了确定MRONJ.的潜在诊断和风险评估生物标志物.
主要方法:
- 微阵列数据分析 (GSE7116) 来自患有或没有MRONJ的多发性骨髓瘤患者和健康对照的外周血液单核细胞.
- 利用差异基因表达分析,基因共同表达网络分析和机器学习算法 (LASSO,脊柱回归) 进行基因识别和验证.
- 进行了功能丰富分析和网络分析,以了解所涉及的生物途径.
主要成果:
- 在MRONJ患者中确定了不同的基因表达模式,包括上调的核糖体/转化通路和抑制的中性粒细胞脱粒化/抗菌防御.
- 关键候选基因 (例如,PDE4B,JAK1,ETS1) 被确定具有高的区分能力 (AUC 0.95-0.99).
- 这些基因在功能上与免疫功能障碍,细胞因子信号传递,NF-κB激活和应激反应有关.
结论:
- MRONJ与系统性免疫-炎症失衡和转化过程的破坏有关.
- 这些已识别的基因为MRONJ诊断和风险分层提供了潜在的新生物标志物.
- 这些发现为MRONJ.的分子病变产生提供了新的见解.
相关概念视频
Stress Response System
605
The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
In the alarm stage, the body's...
Alarm stage
In the alarm stage, the body's...
605
Physiological Foundation of Stress
507
Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
Role of the Sympathetic Nervous System
Adrenaline triggers the...
507
Psychoneuroimmunology: Cardiovascular Disease
363
Psychoneuroimmunology (PNI) is a multidisciplinary field that examines how psychological factors, particularly stress, interact with the immune system and impact physical health. Research in PNI has shown that chronic or traumatic stress can disrupt both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These disruptions contribute to serious health conditions, including cardiovascular diseases.
A key area of focus in PNI is the relationship between stress and coronary...
A key area of focus in PNI is the relationship between stress and coronary...
363
Inflammatory Response
15.8K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
15.8K


