与犬多中心高级别 B 细胞淋巴瘤首次缓解诱导期间早期复发相关的基因表达谱。
Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma.
发表日期:2023 Nov 13
作者:
Hiroto Toyoda, Akiyoshi Tani, Yuko Goto-Koshino, Tomoki Motegi, Mika Sakamoto, Takako Mochizuki, Kei Harada, Tetsuya Kobayashi, Asuka Setoguchi, Yohei Shizuta, Takuya Mizuno, Mitsuhiro Irie, Jun Nakamichi, Hajime Tsujimoto, Aki Ohmi, Ray Fukuoka, Yasukazu Nakamura, Hirotaka Tomiyasu
来源:
GENES & DEVELOPMENT
摘要:
尽管使用基于 CHOP 的化疗方案可在大多数犬多中心高级别 B 细胞淋巴瘤 (mhBCL) 病例中诱导缓解,但有些病例在第一个诱导方案期间出现早期复发。在这项研究中,我们检查了化疗前犬 mhBCL 的基因表达谱,并研究了它们与第一个完整的基于 CHOP 的方案期间早期复发的关系。本研究纳入了 25 例 mhBCL 病例,采用基于 CHOP 的方案作为首次诱导化疗。 16 例完成第一个完整的基于 CHOP 的方案而没有复发(S 组),9 例在化疗期间出现复发(R 组)。对肿瘤淋巴结样本进行 RNA 测序。通过比较S组和R组之间的基因表达谱来提取差异表达基因(DEG),并通过RT-qPCR验证这些基因表达水平的差异。提取的179个DEG包括与趋化因子CC基序配体、T细胞受体信号通路、PD-L1表达和PD-1检查点通路相关的基因。我们关注趋化因子CC基序配体,证实CCL4在R组中显着下调(P=0.039)。我们还关注了与T细胞信号通路相关的基因,证实R组中CD3E(P=0.039)、ITK(P=0.023)和LAT(P=0.023)基因显着上调。目前的结果表明,肿瘤细胞的变化以及肿瘤细胞与免疫细胞之间的相互作用都与诱导首次缓解的化疗效果相关。
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.