Identification of Diagnostic Markers Correlated With HIV+ Immune Non-response Based on Bioinformatics Analysis

Abstract

Background: HIV-infected immunological non-responders (INRs) are characterized by their inability to reconstitute CD4+ T cell pools after antiretroviral therapy. The risk of non-AIDS-related diseases in INRs is increased, and the outcome and prognosis of INRs are inferior to that of immunological responders (IRs). However, few markers can be used to define INRs precisely. In this study, we aim to identify further potential diagnostic markers associated with INRs through bioinformatic analyses of public datasets.Methods: This study retrieved the microarray data sets of GSE106792 and GSE77939 from the Gene Expression Omnibus (GEO) database. After merging two microarray data and adjusting the batch effect, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) resource and Kyoto Encyclopedia of Genes and Genomes (KEGG) resource were conducted to analyze the biological process and functional enrichment. We performed receiver operating characteristic (ROC) curves to filtrate potential diagnostic markers for INRs. Gene Set Enrichment Analysis (GSEA) was conducted to perform the pathway enrichment analysis of individual genes. Single sample GSEA (ssGSEA) was performed to assess scores of immune cells within INRs and IRs. The correlations between the diagnostic markers and differential immune cells were examined by conducting Spearman’s rank correlation analysis. Subsequently, miRNA-mRNA-TF interaction networks in accordance with the potential diagnostic markers were built with Cytoscape. We finally verified the mRNA expression of the diagnostic markers in clinical samples of INRs and IRs by performing RT-qPCR.Results: We identified 52 DEGs in the samples of peripheral blood mononuclear cells (PBMC) between INRs and IRs. A few inflammatory and immune-related pathways, including chronic inflammatory response, T cell receptor signaling pathway, were enriched. FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1 were considered as potential diagnostic markers. ssGSEA results showed that the IRs had significantly higher enrichment scores of seven immune cells compared with IRs. The miRNA-mRNA-TF network was constructed with 97 miRNAs, 6 diagnostic markers, and 26 TFs, which implied a possible regulatory relationship.Conclusion: The six potential crucial genes, FAM120AOS, LTA, FAM179B, JUN, PTMA, and SH3YL1, may be associated with clinical diagnosis in INRs. Our study provided new insights into diagnostic and therapeutic targets.

TTC7B Is a Novel Prognostic-Related Biomarker in Glioma Correlating with Immune Infiltrates and Response to Oxidative Stress by Temozolomide

“…Gene Set Enrichment Analysis. The Gene Set Enrichment Analysis (GSEA) (https://www.gsea-msigdb.org/) includes GO and KEGG pathway analysis, and was undertaken to examine the signaling pathways associated with TTC7B [23]. To evaluate the biological coherence and connections between each anticipated module, which was formed by correlating differently expressed mRNAs with distinct GO subsets, we performed GO analysis.…”

Identification of Potential Diagnostic Genes of HIV-Infected Immunological Non-Responders on Bioinformatics Analysis

“…Besides, the number of CD4 + T cells decreased by 45 cells/µL accompanied by a 5% increase in the percentage of activated CD4 + T cells in the first 3 months of cART treatment. 48 The level of resting dendritic cells is higher in HIV-INRs analyzed by CIBERSORT; however, studies about resting dendritic cells on the immune response in HIV individuals receiving cART are rare and need further research. Meanwhile, CD69 and ZNF207 may regulate the level of resting memory CD4 + T cells, resting mast cells, M2 macrophages, and activated resting dendritic cells, leading to different therapy outcomes in HIV individuals.…”

SH3YL1 Protein Predicts Renal Outcomes in Patients with Type 2 Diabetes

“…Recent reports have revealed the various roles of SH3YL1 in kidney function; these include its interaction with the androgen receptor [44], its association with the immunological non-responsiveness of HIV-infected patients [45], its role in influencing T-cell activation [46], and its involvement in the membrane invagination process of endosomes [47]. Currently, the role of SH3YL1 in various diseases is unclear.…”