Dados do Resumo

Título

Comparative transcriptomics in HTLV-1-associated adult T-cell leukemia suggests insights into the transcriptional profile in viral infection

Introdução

Adult T-cell leukemia (ATL) is an aggressive hematologic malignancy, a lymphoproliferative disease that may or may not be associated with Human T-lymphotropic Virus Type 1 (HTLV-1) infection. Understanding the transcriptional landscape of ATL in different conditions may reveal important insights into cancer pathogenesis, especially that of HTLV in the progression of leukemia in humans.

Objetivo

To compare the ATL gene expression profile in HTLV-infected and uninfected sample groups.

Métodos

49 public transcriptome samples were obtained from NCBI, of which 13 were from patients with ATL (PRJDB10016) and 36 samples from patients with HTLV-1 infection and ATL (PRJNA981458). Data were analyzed in the RStudio platform, using the libraries Dplyr (for table manipulation and treatment), DESeq2 (for differential expression analysis, with p-adjusted parameters < 5% and |Log2 Fold-change > 2|), ggplot2 (data visualization), prComp (PCA analysis) and pROC to select biomarker genes (AUC > 0.9). The gene ontology (GO) of biological processes was predicted by the ClusterProfiler package and the genes selected by ROC were displayed in a heatmap (ComplexHeatmap).

Resultados

Differential expression analysis revealed a majority of underexpressed genes, in relation to overexpressed ones, both with statistical significance. GO analysis showed that a large proportion of genes were involved in the Wnt, IP3-Kinase and ERBB pathways, whose main molecular functions were the activity of transcription and cellular growth factors, cytoskeletal machinery and protein kinases. Through the Heatmap, it was verified that most of the genes with the best AUC values ​​(N = 87) presented underexpression in samples with ATL when compared to the HTLV+ group. The PCA showed that the groups clustered separately, therefore, presenting different expression profiles. We observed greater gene enrichment (400 genes) related to the directed movement of organelles and Wnt signaling, in which the lowest was for the ERBB signaling pathway (~200). In addition, molecular functions of metal ion transport and translation regulation seem strongly related to the differentially expressed genes.

Conclusões

This initial study showed that most cancer-related genes are more highly expressed in the HTLV+ group than in ATL. The analysis suggests that the viral replication cycle influences different pathways in cancer, with significant impacts on the regulation of gene expression. In the case of ATL, HTLV-1 appears to exacerbate the transcription of genes in pathways crucial for tumorigenesis, which may have important effects on disease progression.

Palavras Chave

Adult T-cell leukemia; Human T-lymphotropic Virus Type 1; Transcriptomics