HTLV-1 Replication and Adult T Cell Leukemia Development

Giam, Chou-Zen

doi:10.1007/978-3-030-57362-1_10

Cited by 15 publications

(15 citation statements)

References 146 publications

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“…Functional analyses indicated that the DEGs in the high-risk and low-risk patients identi ed in this study were enriched in several immune-related pathways, including HTLV-1 pathway, which has been implicated in many cancers (32)(33)(34)(35). HTLV-1 encodes two viral genes, Tax and HTLV-1 bZIP factor (HBZ), which play critical roles in viral transcription and promotion of T-cell proliferation.…”

Section: Discussionmentioning

confidence: 83%

Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Liu

Zhang

et al. 2021

Preprint

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Background: Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent regulated cell death, plays an important role in the cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signature in non-small cell lung cancer (NSCLC) remains unknown.Method: The RNA sequencing (RNA-seq) expression data and clinical information of NSCLC were downloaded from The Cancer Genome Atlas (TCGA) database and performed differential analysis. Univariate and multivariate cox regressions were used to identify the ferroptosis-related gene, and receiver operating characteristic (ROC) model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the biological functions of differential genes.Results: A 5-gene signature was constructed to stratify patients into high- and low-risk groups. Compared with patients in the low-risk group, patients in the high-risk group showed significantly poor overall survival (P < 0.001 in the TCGA cohort and P = 0.001 in the GSE13213 cohort). The risk score was an independent predictor for overall survival in multivariate Cox regression analyses (HR > 1, P < 0.01). The 1 year-, 2 year- and 3 year-ROCs were 0.792, 0.644 and 0.641 in TCGA and 0.623, 0.636 and 0.631 in GSE13213, respectively. Functional analysis revealed that immune-related pathways were enriched, and immune status were different between two risk groups. Conclusions: We identified differently expressed immunity- and ferroptosis-related genes that may involve in NSCLC. These genes may predict the overall survival in NSCLC and targeting ferroptosis may be an alternative for clinical therapy.

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Section: Discussionmentioning

confidence: 83%

Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Liu

Zhang

et al. 2021

Preprint

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“…In this study, functional analyses indicated that the identified DEGs were enriched in several immune-related pathways, including HTLV-1 pathway, which has been implicated in many types of cancers [ 34 – 37 ]. HTLV-1 encodes two viral genes, namely Tax and HTLV-1 bZIP factor (HBZ), which play a critical role in viral transcription and promotion of T-cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer

et al. 2021

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Background Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. Methods RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. Results A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. Conclusions We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

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“…An interesting observation in this study was the extensive upregulation of JNK apoptotic pathway in the analysis, confirmed by upregulation of MAPK8 in ATLL samples. The implication of this finding is emphasized in the context of constant activation of NF-KB pathway observed in almost all ATLL clones that normally represses the JNK pathway [ 8 , 50 ]. Furthermore, TNF-induced JNK activation, which is among upregulated DEGs in this study, normally results in apoptosis and cell death in target cells [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Since the initial description of ATLL with aggressive subtypes (acute, lymphomatous, and chronic with unfavorable prognostic factors) having a survival rate of less than one year and despite numerous modalities and therapeutic approaches, the median survival rate has not been improved significantly [ 4 , 6 ]. The oncogenic properties of the viral products are substantiated through countless experiments [ 7 , 8 ]. However, the low prevalence of ATLL among HTLV-1 carriers and the long latency period suggests that factors such as host genetic susceptibility and environmental factors may influence the development of the disease.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma

Shadabi

Delrish

Norouzi

et al. 2021

Infect Agents Cancer

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Background Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients. Methods Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations. Results High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway. Discussion The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.

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HTLV-1 Replication and Adult T Cell Leukemia Development

Cited by 15 publications

References 146 publications

Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Molecular Identification of Immunity- and Ferroptosis-related Gene Signature in Non-small Cell Lung Cancer

Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer

Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma

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