通过生物信息学分析，三个神经系统特异性表达的基因是诊断散发性肌萎缩侧索硬化症的潜在生物标志物。

Three nervous system-specific expressed genes are potential biomarkers for the diagnosis of sporadic amyotrophic lateral sclerosis through a bioinformatic analysis.

机构信息

Department of Neurology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

出版信息

BMC Med Genomics. 2023 Jan 27;16(1):15. doi: 10.1186/s12920-023-01441-x.

DOI:10.1186/s12920-023-01441-x

PMID:36707813

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9881351/

Abstract

BACKGROUND

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease in adults. However, ALS, especially sporadic ALS (sALS), is difficult to diagnose due to the lack of biomarkers.

RESULTS

We used the bioinformatics technology to find the potential biomarker and we found that two hundred seventy-four DEGs were identified and enrichment analysis showed DEGs were involved in nervous system activity, like axon_guidance and the neurotrophin_signaling_pathway. Five nervous system-specific expressed hub genes were further validated by three GEO datasets. APP, LRRK2, and PSEN1 might be potential diagnostic and prognostic biomarkers of sALS, and NEAT1-miR-373-3p/miR-302c-3p/miR-372-3p-APP, circ_0000002-miR-302d-3p/miR-373-3p-APP and XIST-miR-9-5p/miR-30e-5p/miR-671-5p might be potential ceRNA regulatory pathways. APP SNP analysis showed subjects harboring the minor G allele of rs463946, minor G allele of rs466433 and minor C allele of rs364048 had an increased risk of sALS development.

CONCLUSIONS

Our results identified three nervous system-specific expressed hub genes that might be diagnostic and prognostic markers of sALS and APP might be a genetic susceptibility factor contributing to sALS development.

摘要

背景

肌萎缩侧索硬化症（ALS）是成人中最常见的神经退行性疾病。然而，由于缺乏生物标志物，ALS，尤其是散发性 ALS（sALS），难以诊断。

结果

我们使用生物信息学技术找到了潜在的生物标志物，发现了 274 个差异表达基因（DEGs），富集分析表明 DEGs 参与了神经系统活动，如轴突导向和神经营养因子信号通路。通过三个 GEO 数据集进一步验证了五个神经系统特异性表达的枢纽基因。APP、LRRK2 和 PSEN1 可能是 sALS 的潜在诊断和预后生物标志物，而 NEAT1-miR-373-3p/miR-302c-3p/miR-372-3p-APP、circ_0000002-miR-302d-3p/miR-373-3p-APP 和 XIST-miR-9-5p/miR-30e-5p/miR-671-5p 可能是潜在的 ceRNA 调控途径。APP SNP 分析显示，携带 rs463946 minor G 等位基因、rs466433 minor G 等位基因和 rs364048 minor C 等位基因的个体患 sALS 的风险增加。