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

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Mozhgani , S-H , Piran , M , Zarei-Ghobadi , M , Jafari , M , Jazayeri , S-M , Mokhtari-Azad , T , Teymoori-Rad , M , Valizadeh , N , Farajifard , H , Mirzaie , M , Khamseh , A , Rafatpanah , H , Rezaee , S-A & Norouzi , M 2019 , ' An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis ' , Retrovirology , vol. 16 , no. 1 , 46 . https://doi.org/10.1186/s12977-019-0508-8

Title: An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis
Author: Mozhgani, Sayed-Hamidreza; Piran, Mehran; Zarei-Ghobadi, Mohadeseh; Jafari, Mohieddin; Jazayeri, Seyed-Mohammad; Mokhtari-Azad, Talat; Teymoori-Rad, Majid; Valizadeh, Narges; Farajifard, Hamid; Mirzaie, Mehdi; Khamseh, Azam; Rafatpanah, Houshang; Rezaee, Seyed-Abdolrahim; Norouzi, Mehdi
Contributor: University of Helsinki, Research Program in Systems Oncology
Date: 2019-12-30
Language: eng
Number of pages: 11
Belongs to series: Retrovirology
ISSN: 1742-4690
URI: http://hdl.handle.net/10138/312396
Abstract: 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.
Subject: HTLV-1
HTLV-1-associated myelopathy
tropical spastic paraparesis
HAM
TSP
High-throughput data integration
Meta-analysis
Microarray
T-CELL LEUKEMIA
I-ASSOCIATED MYELOPATHY
MESSENGER-RNA EXPRESSION
HTLV-1 PROVIRAL LOAD
GENE-EXPRESSION
INTERFERON-GAMMA
VIRUS
LEUKEMIA/LYMPHOMA
CANCER
PROLIFERATION
3111 Biomedicine
1183 Plant biology, microbiology, virology
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