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

Abstract

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.

Review of Molecular Technologies for Investigating Canine Cancer

“…RNA-Seq of canine mammary tumours ( n = 157) identified three gene expression-based subtypes, one of which was transcriptionally similar to basal-like human breast cancer [ 84 ]. More recently, the gene expression profiles of canine multicentric high-grade B-cell lymphoma ( n = 25) were assessed by RNA-Seq to compare cases where the subjects completed the chemotherapy protocol without relapse, versus those that relapsed during the treatment, and found that both changes in the tumour cells themselves and changes in the immune cell-tumour cell interactions were associated with chemotherapy efficacy [ 92 ]. Finally, other recent studies used RNA-Seq (adapted for small RNA sequencing) to analyse the differential expression of miRNAs in canine diffuse large B-cell lymphoma (6 samples) relative to controls (4 non-neoplastic samples) [ 93 ], and FFPE duodenal samples from canines with intestinal T-cell lymphoma ( n = 9) relative to those with inflammatory bowel disease ( n = 12) and to those with no/minimal inflammation [ 54 ].…”