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

  • TOYODA Hiroto
    Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • TANI Akiyoshi
    Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • GOTO-KOSHINO Yuko
    Veterinary Medical Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • MOTEGI Tomoki
    Boston University School of Medicine, Department of Medicine, Division of Computational Biomedicine, Boston, MA, USA
  • SAKAMOTO Mika
    Genome Informatics Laboratory, National Institute of Genetics, Shizuoka, Japan
  • MOCHIZUKI Takako
    Genome Informatics Laboratory, National Institute of Genetics, Shizuoka, Japan
  • HARADA Kei
    Japan Small Animal Cancer Center, Saitama, Japan
  • KOBAYASHI Tetsuya
    Japan Small Animal Cancer Center, Saitama, Japan
  • SETOGUCHI Asuka
    JASMINE Animal Referral Hospital, Kanagawa, Japan
  • SHIZUTA Yohei
    Bayside Animal Clinic, Kanagawa, Japan
  • MIZUNO Takuya
    Laboratory of Molecular Diagnostics and Therapeutics, Joint Graduate School of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan
  • IRIE Mitsuhiro
    Shikoku Veterinary Medical Center, Kagawa, Japan
  • NAKAMICHI Jun
    Japan Animal Referral Medical Center, Kanagawa, Japan
  • TSUJIMOTO Hajime
    Japan Animal Referral Medical Center, Kanagawa, Japan
  • OHMI Aki
    Veterinary Medical Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • FUKUOKA Ray
    Veterinary Medical Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • NAKAMURA Yasukazu
    Genome Informatics Laboratory, National Institute of Genetics, Shizuoka, Japan
  • TOMIYASU Hirotaka
    Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

抄録

<p>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.</p>

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