Weighted gene co-expression network analysis reveals specific modules and hub genes related to neuropathic pain in dorsal root ganglions

Jing-Yi Du,Yue Guo,Nan Cheng,Xiang Li,Zhuo-Lin Qiu,Zi-Qing Hei,Zheng Zhang

doi:10.1042/bsr20191511

Jing-Yi Du, Yue Guo + Show 5 more

Open Access

https://doi.org/10.1042/bsr20191511

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Journal: Bioscience Reports	Publication Date: Nov 13, 2019
Citations: 8	License type: CC BY 4.0

Affiliation: Sun Yat-sen University

Abstract

Neuropathic pain is a common, debilitating clinical issue. Here, the weighted gene co-expression network analysis (WGCNA) was used to identify the specific modules and hub genes that are related to neuropathic pain. The microarray dataset of a neuropathic rat model induced by tibial nerve transection (TNT), including dorsal root ganglion (DRG) tissues from TNT model (n=7) and sham (n=8) rats, was downloaded from the ArrayExpress database (E-MTAB-2260). The co-expression network modules were identified by the WGCNA package. The protein–protein interaction (PPI) network was constructed, and the node with highest level of connectivity in the network were identified as the hub gene. A total of 1739 genes and seven modules were identified. The most significant module was the brown module, which contained 215 genes that were primarily associated with the biological process (BP) of the defense response and molecular function of calcium ion binding. Furthermore, C–C motif chemokine ligand 2 (Ccl2), Fos and tissue inhibitor of metalloproteinase 1 (Timp1) which were identified as the hub genes in the PPI network and two subnetworks separately. The in vivo studies validated that mRNA and protein levels of Ccl2, Fos and Timp1 were up-regulated in DRG and spinal cord tissues after TNT. The present study offers novel insights into the molecular mechanisms of neuropathic pain in the context of peripheral nerve injury.

Highlights

Neuropathic pain is one of the most frequent forms of pathological pain, and is normally induced by somatosensory system injury or dysfunction [1]
Through the Gene Ontology (GO) functional enrichment analysis (Figure 4), we found that regulation of inflammatory response (GO:0006954, P=2.957e-11), metal ion transmembrane transport activity (GO:0046873, P=4.229e-7) and neuron to neuron synapse (GO:0098984, P=2.144e-14) were the most significant enrichments in biological process (BP), molecular function (MF) and cellular component (CC) groups, respectively
Through the GO annotation enrichment analysis for 215 genes in the brown module, we found most of these genes were implicated in the defense and inflammatory response, which is in line with the results of a previous study that identified the association of genes in the defense and immune process in peripheral blood with pain in patients by Weighted gene co-expression network analysis (WGCNA) [16]

Summary

Introduction

Neuropathic pain is one of the most frequent forms of pathological pain, and is normally induced by somatosensory system injury or dysfunction [1]. 7–10% of the general population is exposed to this condition, and nearly 20% of the population who complain about chronic pain has neuropathic pain [2]. It is still largely unknown which critical genes are responsible for this condition and how the interactions among the critical genes induce the development of neuropathic pain. Weighted gene co-expression network analysis (WGCNA) is a systematical method that was originally reported by Langfelder and Horvath [3] This method is able to identify the correlation patterns of large and high-dimensional gene expression datasets [3]. In the last few years, WGCNA has been widely used to detect co-expressed modules and hub genes in various diseases including cancer [4], coronary artery disease [5] and peripheral arterial disease [6]

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