Zhang Shaoru, Zhang Mengjie, Zhang Lei, Wang Zijie, Tang Shi, Yang Xiaolin, Li Zhizhong, Feng Jinzhou, Qin Xinyue
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Yuzhong District, Chongqing, 400016, China.
Heliyon. 2024 Mar 13;10(6):e28085. doi: 10.1016/j.heliyon.2024.e28085. eCollection 2024 Mar 30.
The knowledge of normal‒appearing cortical gray matter (NAGM) in multiple sclerosis (MS) remains unclear. In this study, we aimed to identify diagnostic biomarkers and explore the immune infiltration characteristics of NAGM in MS through bioinformatic analysis and validation .
Differentially expressed genes (DEGs) were analyzed. Subsequently, the functional pathways of the DEGs were determined. After screening the overlapping DEGs of MS with two machine learning methods, the biomarkers' efficacy and the expression levels of overlapping DEGs were calculated. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) identified the robust diagnostic biomarkers. Additionally, infiltrating immune cell populations were estimated and correlated with the biomarkers. Finally, the characteristics of immune infiltration of NAGM from MS were evaluated.
A total of 98 DEGs were identified. They participated in sensory transduction of the olfactory system, synaptic signaling, and immune responses. Nine overlapping genes were screened by machine learning methods. After verified by ROC curve, four genes, namely ‒, , and , were screened as candidate biomarkers. The mRNA expression of and was significantly lower in MS patients than that in the controls. They were selected as the robust diagnostic biomarkers for male MS patients. and were both positively correlated with memory B cells. Moreover, naive CD4 T cells and monocytes were increased in the NAGM of MS patients compared with those in controls.
Low expressed Y‒linked genes, and , were identified as diagnostic biomarkers for MS in male patients. The inhomogeneity of immune cells in NAGM might exacerbate intricate interplay between the CNS and the immune system in the MS.
多发性硬化症（MS）中正常外观皮质灰质（NAGM）的相关知识仍不清楚。在本研究中，我们旨在通过生物信息学分析和验证来识别诊断生物标志物，并探索MS中NAGM的免疫浸润特征。
分析差异表达基因（DEGs）。随后，确定DEGs的功能途径。用两种机器学习方法筛选MS的重叠DEGs后，计算生物标志物的效能和重叠DEGs的表达水平。定量逆转录聚合酶链反应（qRT-PCR）鉴定出可靠的诊断生物标志物。此外，估计浸润免疫细胞群体并将其与生物标志物相关联。最后，评估MS中NAGM的免疫浸润特征。
共鉴定出98个DEGs。它们参与嗅觉系统的感觉转导、突触信号传导和免疫反应。通过机器学习方法筛选出9个重叠基因。经ROC曲线验证后，筛选出4个基因，即-、、和，作为候选生物标志物。MS患者中和的mRNA表达明显低于对照组。它们被选为男性MS患者的可靠诊断生物标志物。和均与记忆B细胞呈正相关。此外，与对照组相比，MS患者NAGM中的初始CD4 T细胞和单核细胞增加。
低表达的Y连锁基因和被鉴定为男性MS患者的诊断生物标志物。NAGM中免疫细胞的不均匀性可能会加剧MS中中枢神经系统与免疫系统之间复杂的相互作用。
