Dataset Information

Biomarkers mining for spinal cord injury based on integrated multi-transcriptome expression profile data.

ABSTRACT:

Background

This study was aimed to discover more biomarkers associated with spinal cord injury (SCI) by constructing a competing endogenous RNA (ceRNA) network.

Methods

The transcriptome expression profile data related to SCI (GSE45006 GSE20907) were downloaded from GEO database. The differentially expressed RNAs (DERs), including lncRNAs, miRNAs, and mRNAs, between SCI and control groups were selected, which were then performed function enrichment analyses. Following that, a SCI-related ceRNA regulatory network was constructed. PCA analysis was performed on the genes constituting the ceRNA regulatory network directly related to SCI.

Results

In GSE45006 and GSE20907 datasets, there were respectively 3336 and 1453 DERs. Venn analysis showed that there were 429 DERs which had consistent differential expression direction. RGD1564534-miR-29b-5p relation pair and 103 miRNA-target regulatory pairs were integrated to construct the ceRNA regulatory network. Then a SCI-related ceRNA regulatory network including 8 mRNAs of IFNGR1, STAT2, CYBB, NFATC1, FCGR2B, HMOX1, TLR4, and HK2, a lncRNA of RGD1564534, and a miRNA of miR-29b-5p was constructed. Additionally, two pathways, osteoclast differentiation, and HIF-1 signaling pathway, were involved in this network. PCA indicated the samples before and after injury can be significantly distinguished based on the genes in the ceRNA network.

Conclusion

A total of 8 SCI-related mRNAs have been identified in the ceRNA network, including IFNGR1, STAT2, CYBB, NFATC1, FCGR2B, HMOX1, TLR4, and HK2. Moreover, RGD1564534 may serve as ceRNA by competitively binding to miR-29b-5p to regulate the expression of 8 SCI-related mRNAs. Therefore, these genes may serve as key biomarkers of SCI.

SUBMITTER: Gong C

PROVIDER: S-EPMC8051034 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Spinal cord injury (SCI) is one of the most devastating diseases with a high incidence rate around the world. SCI-related neuropathic pain (NeP) is a common complication, whereas its pathomechanism is still unclear. The purpose of this study is to identify key genes and cellular components for SCI-related NeP by an integrated transcriptome bioinformatics analysis. Methods:The gene expression profile of 25 peripheral blood samples from chronic phase SCI patients (E-GEOD-69901) and 337 normal peripheral blood samples were downloaded from ArrayExpress and Genotype-Tissue Expression Portal (GTEx), respectively. A total of 3,368 normal peripheral blood mononuclear cells (PBMC) were download from Sequence Read Archive (SRA713577). Non-parametric tests were used to evaluate the association between all of differential expression genes (DEGs) and SCI-related NeP. CellPhoneDB algorithm was performed to identify the ligand-receptor interactions and their cellular localization among single PBMCs. Transcription factor (TF) enrichment analysis and Gene Set Variation Analysis (GSVA) were used to identify the potential upstream regulatory TFs and downstream signaling pathways, respectively. Co-expression analysis among significantly enriched TFs, key cellular communication genes and differentially expressed signaling pathways were performed to identify key genes and cellular components for SCI-related NeP. Results:A total of 2,314 genes were identified as DEGs between the experimental and the control group. Five proteins (ADRB2, LGALS9, PECAM1, HAVCR2, LRP1) were identified in the overlap of proteins in the significant ligand-receptor interactions of PBMCs and protein-protein interaction (PPI) network based on the DEGs. Only HAVCR2 was significantly associated with NeP (P = 0.005). Besides, the co-expression analysis revealed that TF YY1 had significantly co-expression pattern with cellular communication receptor HAVCR2 (R = -0.54, P < 0.001) in NK cells while HAVCR2 was also co-expressed with mTOR signaling pathway (R = 0.57, P < 0.001). The results of RT-qPCR and external dataset validation supported the signaling axis with the most significant co-expression patterns. Conclusion:In peripheral blood of chronic SCI, HAVCR2 might act as a key receptor on the surface of NK cells and interact with ligand LGALS9 secreted by CD14+ monocytes, inhibiting NK cells through mTOR signaling pathway and ultimately predicting the occurrence of SCI-related NeP. This hypothetical signaling axis may provide prognostic biomarkers and therapeutic targets for SCI-related NeP.