Identification of Y‒linked biomarkers and exploration of immune infiltration of normal-appearing gray matter in multiple sclerosis by bioinformatic analysis

© 2024 The Authors..

Background: 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 in vivo.

Methods: 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.

Results: 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 HLA‒DRB1, RPS4Y1, EIF1AY and USP9Y, were screened as candidate biomarkers. The mRNA expression of RPS4Y1 and USP9Y was significantly lower in MS patients than that in the controls. They were selected as the robust diagnostic biomarkers for male MS patients. RPS4Y1 and USP9Y 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.

Conclusions: Low expressed Y‒linked genes, RPS4Y1 and USP9Y, 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Heliyon - 10(2024), 6 vom: 30. März, Seite e28085

Sprache:

Englisch

Beteiligte Personen:

Zhang, Shaoru [VerfasserIn]
Zhang, Mengjie [VerfasserIn]
Zhang, Lei [VerfasserIn]
Wang, Zijie [VerfasserIn]
Tang, Shi [VerfasserIn]
Yang, Xiaolin [VerfasserIn]
Li, Zhizhong [VerfasserIn]
Feng, Jinzhou [VerfasserIn]
Qin, Xinyue [VerfasserIn]

Links:

Volltext

Themen:

Bioinformatic analysis
Immune infiltration
Journal Article
Multiple sclerosis
Normal-appearing cortical gray matter
Y‒linked gene

Anmerkungen:

Date Revised 23.03.2024

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1016/j.heliyon.2024.e28085

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370052552