The Pyroptosis-Related Signature Predicts Diagnosis and Indicates Immune Characteristic in Major Depressive Disorder.
The Pyroptosis-Related Signature Predicts Diagnosis and Indicates Immune Characteristic in Major Depressive Disorder.
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焦亡相关特征可预测重度抑郁症的诊断并指示免疫特征
DOI：
10.3389/fphar.2022.848939
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发表时间：
2022
影响因子：
5.6
通讯作者：
Gao, Wenqi
中科院分区：
文献类型：
--
作者：
Deng, Zhifang;Liu, Jue;He, Shen;Gao, Wenqi
细胞凋亡是一种程序性细胞死亡的炎症形式。然而，脓毒性相关基因（PS基因）在抑郁症（MDD）中的作用尚不清楚。本研究建立了一种基于PS基因的MDD诊断模型，并探讨了与焦亡相关的病理机制。首先，我们从GSE 98793数据集中获得了23个在健康对照和MDD病例之间差异表达的PS基因。MDD患者与健康对照组之间免疫细胞浸润和免疫相关通路的富集存在明显差异。然后，通过随机森林（RF）和最小绝对收缩和选择算子（LASSO）分析，构建了由8个PS基因（GPER 1、GZMA、HMGB 1、IL 1 RN、NLRC 4、NLRP 3、UTS 2和CAPN 1）组成的MDD诊断模型。ROC曲线分析表明，该模型具有良好的诊断性能，AUC = 0.795（95%CI 0.721-0.868）。随后，构建了基于23个PS差异表达基因的一致性聚类方法，将所有MDD病例分为两个不同的焦亡亚型（聚类A和B），这两个亚型具有不同的免疫学和生物学特性。进行主成分分析（PCA）算法来计算每个样本的焦亡评分（“PS评分”），以量化焦亡调节亚型。B组抑郁症患者的“PS评分”高于A组。此外，我们还发现B簇中MDD患者的11种干扰素（IFN）-α亚型表达水平较低。总之，焦亡可能在MDD中发挥重要作用，并可以为MDD的诊断和潜在机制提供新的见解。
Pyroptosis is recently identified as an inflammatory form of programmed cell death. However, the roles of pyroptosis-related genes (PS genes) in major depressive disorder (MDD) remain unclear. This study developed a novel diagnostic model for MDD based on PS genes and explored the pathological mechanisms associated with pyroptosis. First, we obtained 23 PS genes that were differentially expressed between healthy controls and MDD cases from GSE98793 dataset. There were obvious variation in immune cell infiltration profiles and immune-related pathway enrichment between healthy controls and MDD cases. Then, a novel diagnostic model consisting of eight PS genes (GPER1, GZMA, HMGB1, IL1RN, NLRC4, NLRP3, UTS2, and CAPN1) for MDD was constructed by random forest (RF) and least absolute shrinkage and selection operator (LASSO) analyses. ROC analysis revealed that our model has good diagnostic performance, AUC = 0.795 (95% CI 0.721–0.868). Subsequently, the consensus clustering method based on 23 differentially expressed PS genes was constructed to divide all MDD cases into two distinct pyroptosis subtypes (cluster A and B) with different immune and biological characteristics. Principal component analysis (PCA) algorithm was performed to calculate the pyroptosis scores (“PS-scores”) for each sample to quantify the pyroptosis regulation subtypes. The MDD patients in cluster B had higher “PS-scores” than those in cluster A. Furthermore, we also found that MDD patients in cluster B showed lower expression levels of 11 interferon (IFN)-α isoforms. In conclusion, pyroptosis may play an important role in MDD and can provide new insights into the diagnosis and underlying mechanisms of MDD.
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影响因子：
10.6
作者：
Leday GGR;Vértes PE;Richardson S;Greene JR;Regan T;Khan S;Henderson R;Freeman TC;Pariante CM;Harrison NA;MRC Immunopsychiatry Consortium;Perry VH;Drevets WC;Wittenberg GM;Bullmore ET
通讯作者：
Bullmore ET
DOI：
10.1198/tas.2011.11052
发表时间：
2011-11-01
期刊：
The American statistician
影响因子：
--
作者：
Martinez JG;Carroll RJ;Müller S;Sampson JN;Chatterjee N
通讯作者：
Chatterjee N
影响因子：
3
作者：
Kursa MB
通讯作者：
Kursa MB
影响因子：
3.2
作者：
Lépine JP;Briley M
通讯作者：
Briley M
影响因子：
3.8
作者：
Lindblad, Anna;Persson, Katarina;Demirel, Isak
通讯作者：
Demirel, Isak