Identification of Biomarkers for Sarcoidosis and Tuberculosis of the Lung Using Systematic and Integrated Analysis

Abstract

BACKGROUND Sarcoidosis (SARC) is a multisystem inflammatory disease of unknown etiology and pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis. Both of these diseases affect lungs and lymph nodes and share similar clinical manifestations. However, the underlying mechanisms for the similarities and differences in genetic characteristics of SARC and PTB remain unclear. MATERIAL AND METHODS Three datasets (GSE16538, GSE20050, and GSE19314) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SARC and PTB were identified using GEO2R online analyzer and Venn diagram software. Functional enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) and R packages. Two protein-protein interaction (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes database, and module analysis was performed using Cytoscape. Hub genes were identified using area under the receiver operating characteristic curve analysis. RESULTS We identified 228 DEGs, including 56 common SARC-PTB DEGs (enriched in interferon-gamma-mediated signaling, response to gamma radiation, and immune response) and 172 SARC-only DEGs (enriched in immune response, cellular calcium ion homeostasis, and dendritic cell chemotaxis). Potential biomarkers for SARC included CBX5, BCL11B, and GPR18. CONCLUSIONS We identified potential biomarkers that can be used as candidates for diagnosis and/or treatment of patients with SARC.

Figure 1

Identification of 56 common SARC-PTB DEGs in the 2 datasets (GSE16538 and GSE20050), and 172 SARC-only DEGs in GSE16538 through Venn diagrams software. Different color meant different datasets. (A) 55 DEGs were upregulated in the 2 datasets, 142 DEGs were in GSE16238 (logFC >0). (B) 1 DEG was downregulated in 2 datasets, 30 DEGs in GSE16238 (logFC <0). Different color meant different datasets. DEGs – differentially expressed genes; SARC – sarcoidosis; PTB – pulmonary tuberculosis.

Figure 2

GO terms of overlapped SARC-only DEGs. (A–C) Upregulated genes. (D–F) Downregulated genes. (A, D), biological process; (B, E), cellular component; (C, F), molecular function. GO – Gene ontology; DEGs – differentially expressed genes; SARC – sarcoidosis.

Figure 3

PPI network of SARC-PTB common DEGs and modules analysis. (A) PPI network of SARC-PTB common DEGs; (B) the only one module of PPI network. The red nodes represent the upregulated DEGs. The blue nodes represent the downregulated DEGs. The nodes meant proteins; the edges meant the interaction of proteins. PPI – protein–protein interaction; DEGs – differentially expressed genes; SARC – sarcoidosis; PTB – pulmonary tuberculosis.

Figure 4

PPI network of SARC-only DEGs and modules analysis. (A) PPI network of SARC-only DEGs; (B–D) the top 3 modules of PPI network. The red nodes represent the upregulated DEGs. The blue nodes represent the downregulated DEGs. The nodes meant proteins; the edges meant the interaction of proteins. PPI – protein–protein interaction; DEG – differentially expressed genes; SARC – sarcoidosis.

Figure 5

The diagnosis information of the 13 hub genes. The ROC curves were used to identify the diagnosis information of the 13 hub genes and, except CCL5. CBX5, BCL11B and GPR18 had a significantly diagnostic value (AUC >0.80). ROC curve – receiver operating characteristic curve; AUC – the area under the ROC curve.