BackgroundHuman 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.ResultsHigh-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).ConclusionsHigh-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.

中文翻译：

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深入了解 HTLV-1 相关脊髓病/热带痉挛性截瘫 (HAM/TSP) 发病机制；来自高通量数据集成和荟萃分析的证据

研究背景人类T淋巴细胞病毒1相关性脊髓病/热带痉挛性截瘫（HAM/TSP）是一种严重影响脊髓的中枢神经系统进行性疾病，但其发病途径和可靠的生物标志物尚未明确。本研究旨在采用高通量荟萃分析来寻找可能参与 HAM/TSP 发病机制的主要基因。结果高通量统计分析确定了正常与 AC、正常与非正常的 832、49 和 22 个差异表达基因。 HAM/TSP 和 AC 分别与 HAM/TSP 组比较。DEG 之间的蛋白质-蛋白质相互作用在 STRING 中得到鉴定，进一步的网络分析分别强调了正常组与 HAM/TSP 组以及 AC 组与 HAM/TSP 组的 24 个和 6 个中心基因。此外，针对正常与 AC，鉴定了四个具有生物学意义的模块，包括 251 个基因。生物网络分析表明，中枢基因参与许多重要通路，如正常组与 HAM/TSP 组中的 JAK-STAT 信号通路、干扰素、白细胞介素和免疫通路以及 RNA 代谢、病毒 mRNA 翻译、人类 T 细胞白血病病毒1 感染，以及正常组与 AC 组的细胞周期。此外，通过网络分析鉴定了 STAT1、TAP1 和 PSMB8 三个主要基因。实时 PCR 显示 HAM/TSP 样本中 STAT1 较 AC 和正常样本显着下调（分别为 P = 0.01 和 P = 0.02），HAM/TSP 样本中 PSMB8 较 AC 和正常样本上调（分别为 P = 0.01 和 P = 0.02）。 P = 0.04 和 P = 0.01，分别），并且 HAM/TSP 样本中 TAP1 的下调比 AC 和正常样本中的 TAP1 下调（分别为 P = 0.008 和 P = 0.02）。三组中辅助性T细胞和细胞毒性T淋巴细胞的百分比没有显着差异（P = 0.55和P = 0.12）。结论高通量数据整合揭示了参与病毒感染和免疫系统重要途径的新枢纽基因。需要进行全面的研究来提高我们对复杂疾病的发病机制和生物标志物的了解。