Comprehensive analysis of gene expression profiles reveals novel candidates of chemotherapy resistant factors in canine lymphoma

Suenaga, Miyu; Tomiyasu, Hirotaka; Watanabe, Masao; Ogawa, Kohji; Motegi, Tomoki; Goto‐Koshino, Yuko; Ohno, Koichi; Sugano, Sumio; Skorupski, Katherine A; Tsujimoto, Hajime

doi:10.1016/j.tvjl.2017.10.002

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…Based on these evidences, it is possible that these miRNAs might be associated with the drug resistance in lymphoid tumours via modification of target gene expressions in parent tumour cells. In our previous report, in addition, expression of genes related to immune responses and inflammatory reactions was decreased in tumour tissues obtained from canine lymphoma patients at chemotherapy resistant phases [37]. Therefore, it is also possible that these miRNAs within exosomes might cause inactivation of immune response and inflammatory reaction in lymphoid tumour tissues.…”

Section: Discussionmentioning

confidence: 95%

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

Asada

Tomiyasu

Uchikai³

et al. 2019

PLoS ONE

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Exosomes are small extracellular vesicles released from almost all cell types, which play roles in cell-cell communication. Recent studies have suggested that microenvironmental crosstalk mediated by exosomes is an important factor in the escape of tumour cells from the anti-tumour immune system in human haematopoietic malignancies. Here, we conducted comprehensive analysis of the miRNA and protein profiles within the exosomes released from four canine lymphoid tumour cell lines as a model of human lymphoid tumours. The results showed that the major miRNAs and proteins extracted from the exosomes were similar among the four cell lines. However, the miRNA profiles differed among the exosomes of each cell line, which corresponded to the expression patterns of the parent cells. In the comparison of the amounts of miRNAs and proteins among the cell lines, those of three miRNAs (miR-151, miR-8908a-3p, and miR-486) and CD82 protein differed between exosomes derived from vincristine-sensitive and resistant cell lines. Further investigations are needed to elucidate the biological functions of the exosomal contents in the microenvironmental crosstalk of lymphoid tumours.

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Section: Discussionmentioning

confidence: 95%

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

Asada

Tomiyasu

Uchikai³

et al. 2019

PLoS ONE

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“…Transcriptomic analysis revealed the overexpression of immunosuppressive factors and inflammatory chemokines in relapsed/refractory DLBCL cases when compared to chemotherapy-sensitive DLBCL cases [ 16 ]. In veterinary medicine, our previous study showed that the expression levels of the genes associated with immune responses were changed in canine mhBCL when cases acquired resistance to chemotherapy [ 35 ]. These previous findings suggest that interactions between tumor cells and the tumor microenvironment, including T cells, may be involved in the response to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, their comparison between groups by RT-qPCR could not be conducted due to their low expression levels. Moreover, it was previously shown that the genes related to inflammatory responses were down-regulated in dogs with chemotherapy-resistant lymphoma [ 35 , 38 ]. These findings suggest a potential association between decreased anti-tumor immune response and early relapse as T-cells in the tumor microenvironment may experience cellular exhaustion in the R-group.…”

Section: Discussionmentioning

confidence: 99%

“…Other drug-resistant factors, which were previously reported in human medicine, were not associated with chemoresistance in canine lymphoma in the same previous study [ 39 ]. Therefore, we investigated novel candidate genes associated with the acquisition of chemotherapy resistance by comparing gene expression profiles in canine mhBCL cases between before and after the acquisition of chemotherapy resistance [ 35 , 38 ]. Other studies have shown that the expression of checkpoint molecule is increased when canine lymphoma cell lines acquired resistance to chemotherapeutic agents [ 20 ].…”

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confidence: 99%

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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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“…RT-PCR technology has been used to study the differential gene expression profiles and differentially expressed genes (DEGs) in dogs with multicentric high-grade B-cell lymphoma (26), at the chemotherapy-sensitive and -resistant stages. A total of 57 DEGs were identified and 16 of them were associated with chemotherapy-resistance.…”

Section: Transcriptomicsmentioning

confidence: 99%

Genomics and transcriptomics in veterinary oncology (Review)

Harrison

Loukopoulos

2021

Oncol Lett

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The sequencing of the canine genome, combined with additional genomic technologies, has created opportunities for research linking veterinary genomics with naturally occurring cancer in dogs. Also, as numerous canine cancers have features in common with human cancers, comparative studies can be performed to evaluate the use of cancers in dogs as models for human cancer. There have been several reviews of veterinary genomics but, to the best of our knowledge, there has been no comprehensive review of the literature of canine cancer genomics. PubMed and CAB Abstracts databases were searched to retrieve relevant literature using the search terms 'veterinary', 'cancer' or 'oncology', and 'genomics' or 'transcriptomics'. Results were manually assessed and grouped based on the techniques used, the cancer type investigated and genomic lesions targeted. The search resulted in the retrieval of 44 genomic and transcriptomic studies, with the most common technique employed being comparative genomic hybridization. Across both fields, the most commonly studied cancer type was canine osteosarcoma. Genomic and transcriptomic aberrations in canine cancer often reflected those reported in the corresponding human cancers. Analysis of the literature indicated that employing genomic and transcriptomic technologies has been instrumental in developing the understanding of the origin, development and pathogenesis of several canine cancers. However, their use in canine oncology is at an early phase, and there appears to be comparatively little understanding of certain canine cancer types in contrast to their human forms. Aberrations detected in all tumors were tabulated, and the results for osteosarcoma, lymphoma and leukemia, mast cell tumor, transmissible venereal tumor and urothelial carcinoma discussed in detail. Contents 1. Introduction 2. Materials and methods 3. Genomics 4. Transcriptomics 5. Studies pertaining to the most common cancer types 6. Review articles 7. Conclusions

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Comprehensive analysis of gene expression profiles reveals novel candidates of chemotherapy resistant factors in canine lymphoma

Cited by 4 publications

References 8 publications

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

Comprehensive analysis of miRNA and protein profiles within exosomes derived from canine lymphoid tumour cell lines

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

Genomics and transcriptomics in veterinary oncology (Review)

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