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非酒精性脂肪性肝病各阶段关键标志物的鉴定:整合生物信息学分析与实验验证。

Identification of key markers for the stages of nonalcoholic fatty liver disease: An integrated bioinformatics analysis and experimental validation.

机构信息

Laboratorio de Fibrosis y Cáncer, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Ex Hacienda de Aguilera S/N, Sur, San Felipe del Agua 68020, Oaxaca, Mexico.

International Laboratory for Human Genome Research, Laboratorio Internacional de Investigación sobre el Genoma Humano (LIIGH), Universidad Nacional Autónoma de México (UNAM), 3001 Boulevard Juriquilla 76230, Querétaro, Mexico.

出版信息

Dig Liver Dis. 2024 Nov;56(11):1887-1896. doi: 10.1016/j.dld.2024.05.010. Epub 2024 Jun 1.

DOI:10.1016/j.dld.2024.05.010
PMID:38824040
Abstract

BACKGROUND

The identification of biomarkers for the early diagnosis of nonalcoholic fatty liver disease (NAFLD) is urgently needed. Here, we aimed to identify NAFLD biomarkers in the early stages of steatosis (SS) and nonalcoholic steatohepatitis (NASH) based on differential gene expression from bioinformatics data.

METHODS

A meta-analysis was performed from transcriptomic databases retrieved from public repositories containing data from biopsies of patients at various stages of NAFLD development. The status of the selected molecules was validated in the serum of patients with NAFLD by ELISA.

RESULTS

We identified 121 differentially expressed genes (DEGs) associated with SS and 402 associated with NASH. Gene Ontology (GO) enrichment revealed that the altered genes were primarily associated with dysfunction of primary cellular processes, and pathway analyses were mainly related to cholesterol metabolism. We identified ACSS2, PCSK9, and CYP7A1 as candidate biomarkers for SS and ANGPTL3, CD36, CYP51A1, FASN, FAS, FDFT1, and LSS as candidate biomarkers for NASH.

CONCLUSIONS

By experimental validation of bioinformatics data from patients with NAFLD, we identified promising biomarkers for detecting SS and NASH that might be useful for screening and diagnosing early NAFLD stages in humans.

摘要

背景

迫切需要鉴定用于非酒精性脂肪性肝病 (NAFLD) 早期诊断的生物标志物。在此,我们旨在根据生物信息学数据中差异表达基因,鉴定脂肪变性 (SS) 和非酒精性脂肪性肝炎 (NASH) 早期阶段的 NAFLD 生物标志物。

方法

从包含 NAFLD 发展各个阶段患者活检数据的公共数据库中转录组数据库中进行荟萃分析。通过 ELISA 法在 NAFLD 患者血清中验证所选分子的状态。

结果

我们鉴定出与 SS 相关的 121 个差异表达基因 (DEGs) 和与 NASH 相关的 402 个 DEGs。基因本体论 (GO) 富集分析显示,改变的基因主要与原发性细胞功能障碍有关,途径分析主要与胆固醇代谢有关。我们将 ACSS2、PCSK9 和 CYP7A1 鉴定为 SS 的候选生物标志物,将 ANGPTL3、CD36、CYP51A1、FASN、FAS、FDFT1 和 LSS 鉴定为 NASH 的候选生物标志物。

结论

通过对 NAFLD 患者的生物信息学数据进行实验验证,我们鉴定出了用于检测 SS 和 NASH 的有前途的生物标志物,这些标志物可能有助于筛查和诊断人类早期 NAFLD 阶段。

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