An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Autor: Mohieddin Jafari, Mehdi Norouzi, Mehdi Mirzaie, Sayed-Hamidreza Mozhgani, Seyed-Abdolrahim Rezaee, Majid Teymoori-Rad, Hamid Farajifard, Houshang Rafatpanah, Mohadeseh Zarei Ghobadi, Narges Valizadeh, Seyed Mohammad Jazayeri, Talat Mokhtari-Azad, Mehran Piran, Azam Khamseh
Přispěvatelé: Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Microarray
Gene Expression
Pathogenesis
Myelopathy
0302 clinical medicine
Proviruses
Interferon
immune system diseases
Tropical spastic paraparesis
Cytotoxic T cell
Gene Regulatory Networks
MESSENGER-RNA EXPRESSION
1183 Plant biology
microbiology
virology
GENE-EXPRESSION
Human T-lymphotropic virus 1
tropical spastic paraparesis
0303 health sciences
LEUKEMIA/LYMPHOMA
T-CELL LEUKEMIA
PROLIFERATION
food and beverages
virus diseases
T-Lymphocytes
Helper-Inducer
Viral Load
TSP
CANCER
Paraparesis
Tropical Spastic
3. Good health
Infectious Diseases
Data Interpretation
Statistical
030220 oncology & carcinogenesis
VIRUS
medicine.drug
HTLV-1 PROVIRAL LOAD
lcsh:Immunologic diseases. Allergy
endocrine system
Biology
Virus
03 medical and health sciences
Immune system
Virology
medicine
Humans
I-ASSOCIATED MYELOPATHY
030304 developmental biology
INTERFERON-GAMMA
Research
HTLV-1-associated myelopathy/tropical spastic paraparesis
PSMB8
Microarray Analysis
medicine.disease
High-Throughput Screening Assays
HAM
Meta-analysis
HTLV-1
Immunology
High-throughput data integration
3111 Biomedicine
TAP1
HAM/TSP
lcsh:RC581-607
HTLV-1-associated myelopathy
030217 neurology & neurosurgery
T-Lymphocytes
Cytotoxic
Zdroj: Retrovirology, Vol 16, Iss 1, Pp 1-11 (2019)
Retrovirology
DOI: 10.1101/754697
Popis: Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein–protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.
Databáze: OpenAIRE
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