Meta-Analysis of HTLV-1-Infected Patients Identifies CD40LG and GBP2 as Markers of ATLL and HAM/TSP Clinical Status: Two Genes Beat as One

被引：6

作者：

Fukutani, Eduardo Rocha ^{[1
]}

Pereira Ramos, Pablo Ivan ^{[1
]}

Kasprzykowski, Jose Irahe ^{[1
]}

Azevedo, Lucas Gentil ^{[1
]}

de Souza Rodrigues, Moreno Magalhaes ^{[2
]}

de Oliveira Pimenta Lima, Joao Victor ^{[1
]}

Santos de Araujo Junior, Helton Fabio ^{[1
]}

Fukutani, Kiyoshi Ferreira ^{[1
,3
,4
]}

Lopo de Queiroz, Artur Trancoso ^{[1
]}

机构：

[1] Fiocruz MS, Ctr Data & Knowledge Integrat Hlth CIDACS, Inst Goncalo Moniz, Salvador, BA, Brazil

[2] FIOCRUZ RO, Lab Anal & Visualizacao Dados, Salvador, BA, Brazil

[3] Multinatl Org Network Sponsoring Translat & Epide, Fundacao Jose Silveira, FJS, Salvador, BA, Brazil

[4] Fac Tecnol & Ciencias, Fac Med, Salvador, BA, Brazil

来源：

FRONTIERS IN GENETICS | 2019年 / 10卷

关键词：

human T-lymphotropic virus 1; bioinformatics; biomarkers; adult T-cell lymphoma; leukemia; HTLV-1 associated myelopathy; tropical spastic paraparesis; meta-analysis; T-CELL LEUKEMIA; I-ASSOCIATED MYELOPATHY; SPASTIC PARAPARESIS; EXPRESSION; CLASSIFICATION; LYMPHOMA; FEATURES; PATHWAY; DISEASE; RISK;

D O I：

10.3389/fgene.2019.01056

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Human T-lymphotropic virus 1 (HTLV-1) was the first recognized human retrovirus. Infection can lead to two main symptomatologies: adult T-cell lymphoma/leukemia (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Each manifestation is associated with distinct characteristics, as ATLL presents as a leukemia-like disease, while HAM/TSP presents as severe inflammation in the central nervous system, leading to paraparesis. Previous studies have identified molecules associated with disease development, e.g., the downregulation of Foxp3 in Treg cells was associated with increased risk of HAM/TSP. In addition, elevated levels of CXCL10, CXCL9, and Neopterin in cerebrospinal fluid also present increased risk. However, these molecules were only associated with specific patient groups or viral strains. Furthermore, the majority of studies did not jointly compare all clinical manifestations, and robust analysis entails the inclusion of both ATLL and HAM/TSP. The low numbers of samples also pose difficulties in conducting gene expression analysis to identify specific molecular relationships. To address these limitations and increase the power of manifestation-specific gene associations, meta-analysis was performed using publicly available gene expression data. The application of supervised learning techniques identified alterations in two genes observed to act in tandem as potential biomarkers: GBP2 was associated with HAM/TSP, and CD40LG with ATLL. Together, both molecules demonstrated high sample-classification accuracy (AUC values: 0.88 and 1.0, respectively). Next, other genes with expression correlated to these genes were identified, and we attempted to relate the enriched pathways identified with the characteristic of each clinical manifestation. The present findings contribute to knowledge surrounding viral progression and suggest a potentially powerful new tool for the molecular classification of HTLV-associated diseases.

引用

页数：9