Transcriptomic meta-analysis identifies gene expression characteristics in various samples of HIV-infected patients with nonprogressive disease

Journal of Translational Medicine

Research

Ya-Jing Fu¹  Xian Wu¹  Hong Shang¹  Yong-Jun Jiang¹  Le-Le Zhang¹  Zi-Ning Zhang¹ 

[1] Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, No 155, Nanjingbei Street, Heping District, 110001, Shenyang, Liaoning Province, China;Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China;

关键词: HIV-1;    LTNP;    EC;    Integrative transcriptome analyses;    Microarray;    Meta-analysis;   

DOI  :  10.1186/s12967-017-1294-5

 received in 2017-05-23, accepted in 2017-09-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundA small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4+ T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers.MethodsUsing the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed genes (DEGs) in nonprogressors and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DEGs identified in the meta-analysis. Five microarray datasets (81 cases and 98 controls in total), including whole blood, CD4+ and CD8+ T cells, were collected for meta-analysis.ResultsWe determined that nonprogressors have reduced expression of important interferon-stimulated genes (ISGs), CD38, lymphocyte activation gene 3 (LAG-3) in whole blood, CD4+ and CD8+ T cells. Gene ontology (GO) analysis showed a significant enrichment in DEGs that function in the type I interferon signaling pathway. Upregulated pathways, including the PI3K-Akt signaling pathway in whole blood, cytokine–cytokine receptor interaction in CD4+ T cells and the MAPK signaling pathway in CD8+ T cells, were identified in nonprogressors compared with progressors. In each metabolic functional category, the number of downregulated DEGs was more than the upregulated DEGs, and almost all genes were downregulated DEGs in the oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle in the three types of samples.ConclusionsOur transcriptomic meta-analysis provides a comprehensive evaluation of the gene expression profiles in major blood types of nonprogressors, providing new insights in the understanding of HIV pathogenesis and developing strategies to delay HIV disease progression.

【 授权许可】

CC BY   
© The Author(s) 2017