Genome-wide DNA methylation and RNA-seq analyses identify genes and pathways associated with doxorubicin resistance in a canine diffuse large B-cell lymphoma cell line

Hsu, Chia-Hsin; Tomiyasu, Hirotaka; Liao, Chi-Hsun; Lin, Chen-Si

doi:10.1371/journal.pone.0250013

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…To this direction, epigenetic modifications are also important regulators of gene expression and drug response. Although the involvement of DNA methylation to drug pharmacological effects remains unclear, there is strong evidence associating cancer treatment resistance in altered DNA methylation profiles [65,66]. Systematic analysis of DNA methylation profiles across cancer cell lines will provide a valuable resource for comprehensive insights of the gene-drug interactions.…”

Section: Discussionmentioning

confidence: 99%

Unraveling Drug Response from Pharmacogenomic Data to Advance Systems Pharmacology Decisions in Tumor Therapeutics

Kardamiliotis

Karanatsiou

Aslanidou

et al. 2022

Future Pharmacology

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The availability of systematic drug response registries for hundreds cell lines, coupled with the comprehensive profiling of their genomes/transcriptomes enabled the development of computational methods that investigate the molecular basis of drug responsiveness. Herein, we propose an automated, multi-omics systems pharmacology method that identifies genomic markers of anti-cancer drug response. Given a cancer type and a therapeutic compound, the method builds two cell line groups on the antipodes of the drug response spectrum, based on the outer quartiles of the maximum micromolar screening concentration. The method intersects cell lines that share common features in their mutation status, gene expression levels or copy number variants, and a pool of drug response biomarkers (core genes) is built, using genes with mutually exclusive alterations in the two cell line groups. The relevance with the drug target pathways is then quantified, using the combined interaction score of the core genes and an accessory protein network having strong, physical/functional interactions. We demonstrate the applicability and effectiveness of our methodology in three use cases that end up in known drug-gene interactions. The method steps into explainable bioinformatics approaches for novel anticancer drug-gene interactions, offering high accuracy and increased interpretability of the analysis results. Availability: https://github.com/PGxAUTH/PGxGDSC.

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Section: Discussionmentioning

confidence: 99%

Unraveling Drug Response from Pharmacogenomic Data to Advance Systems Pharmacology Decisions in Tumor Therapeutics

Kardamiliotis

Karanatsiou

Aslanidou

et al. 2022

Future Pharmacology

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“…Although it is often difficult to determine this association due to the variability of peak callers, some studies have shown its importance in, for example, defining genes and pathways associated with doxorubicin resistance. 241 Some studies have successfully used data on DNA sequence variations (e.g. in the differentiation of MCL subtypes), 242 protein or metabolite abundance, and clinical information.…”

Section: Future Perspectives: Paving the Way For Precision Medicine W...mentioning

confidence: 99%

Epigenetic targets in B- and T-cell lymphomas: latest developments

Ribeiro

Sánchez-Vinces

Mondragón

et al. 2023

Therapeutic Advances in Hematology

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Non-Hodgkin’s lymphomas (NHLs) comprise a diverse group of diseases, either of mature B-cell or of T-cell derivation, characterized by heterogeneous molecular features and clinical manifestations. While most of the patients are responsive to standard chemotherapy, immunotherapy, radiation and/or stem cell transplantation, relapsed and/or refractory cases still have a dismal outcome. Deep sequencing analysis have pointed out that epigenetic dysregulations, including mutations in epigenetic enzymes, such as chromatin modifiers and DNA methyltransferases (DNMTs), are prevalent in both B- cell and T-cell lymphomas. Accordingly, over the past decade, a large number of epigenetic-modifying agents have been developed and introduced into the clinical management of these entities, and a few specific inhibitors have already been approved for clinical use. Here we summarize the main epigenetic alterations described in B- and T-NHL, that further supported the clinical development of a selected set of epidrugs in determined diseases, including inhibitors of DNMTs, histone deacetylases (HDACs), and extra-terminal domain proteins (bromodomain and extra-terminal motif; BETs). Finally, we highlight the most promising future directions of research in this area, explaining how bioinformatics approaches can help to identify new epigenetic targets in B- and T-cell lymphoid neoplasms.

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“…Other studies have shown that the expression of checkpoint molecule is increased when canine lymphoma cell lines acquired resistance to chemotherapeutic agents [21]. Additionally, it has been suggested that TGF-beta signaling pathway may be involved in resistance to doxorubicin in canine lymphoma cell lines [22].…”

Section: Introductionmentioning

confidence: 99%

“…Other studies have shown that the expression of checkpoint molecule is increased when canine lymphoma cell lines acquired resistance to chemotherapeutic agents [ 20 ]. Additionally, it has been suggested that TGF-beta signaling pathway may be involved in resistance to doxorubicin in canine lymphoma cell lines [ 21 ]. However, there has been no study that investigated any molecules associated with early relapse during the first induction of remission in canine mhBCL cases.…”

mentioning

confidence: 99%

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma

TOYODA,

TANI,

GOTO-KOSHINO

et al. 2024

The Journal of Veterinary Medical Science

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Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group ( P =0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E ( P =0.039), ITK ( P =0.023), and LAT ( P =0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

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Genome-wide DNA methylation and RNA-seq analyses identify genes and pathways associated with doxorubicin resistance in a canine diffuse large B-cell lymphoma cell line

Cited by 6 publications

References 38 publications

Unraveling Drug Response from Pharmacogenomic Data to Advance Systems Pharmacology Decisions in Tumor Therapeutics

Unraveling Drug Response from Pharmacogenomic Data to Advance Systems Pharmacology Decisions in Tumor Therapeutics

Epigenetic targets in B- and T-cell lymphomas: latest developments

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma

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