Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia

Author:

Yao Menghui,Wang Shuolin,Han Yingdong,Zhao He,Yin Yue,Zhang Yun,Zeng Xuejun

Abstract

Abstract Background Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. Methods The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. Results The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer–Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. Conclusion Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

Funder

National Natural Science Foundation of China

2019 Discipline Development Project of Peking Union Medical College

National High Level Hospital Clinical Research Funding

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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