PSVIII-6 Analysis of potential biomarkers in dogs diagnosed with three common cancer types shows association with B cell functions.

Abstract One in four dogs will be diagnosed with malignancies in their lifetime. Malignancies can be unpredictable and grow at various rates depending on the type, making it the leading cause of death in adult dogs. Therefore, the objective of this retrospective study was to explore similarities in mRNA abundance between prevalent canine cancer types. Blood samples for mRNA analysis from 36 dogs were collected at end of life, when quality of life had declined. All study procedures were approved by the Hill’s Institutional Animal Care and Use Committee. Samples were from dogs without cancer (n=18; control), diagnosed with hemangiosarcoma (n=6; HSA), diagnosed with transitional cell carcinoma (n=6; TCC), and diagnosed with lymphosarcoma (n=6; LSA). Gene expression was examined using the NanoString nCounter® platform and data analysis was performed using the nSolver software provided by NanoString. Each cancer group was analyzed against the control group. Seventy-nine significant (P< 0.05 and a fold change of >1.5 or < -1.5) genes were identified including 29 from the HSA group, 38 from the TCC group, and 24 from the LSA group. Of the 79 significant genes, 9 genes overlapped between the HSA and TCC groups, 3 overlapped between the HSA and LSA groups, but there were no genes that overlapped between the LSA and TCC groups. Of the 12 overlapping genes, 6 genes identified in both the HSA and TCC groups are involved with B cell functions. CD22 molecule abundance was increased (P< 0.05) by 2.18-fold in the HSA group and 2.28-fold in the TCC group. Tumor necrosis factor receptor superfamily member 13C abundance was increased (P< 0.05) by 2.04-fold in the HSA group and by 2.45-fold in the TCC group. Membrane spanning 4-domains A1 abundance was increased (P< 0.05) by 1.88-fold in the HSA group and by 2.23-fold in the TCC group. B cell linker abundance was increased (P< 0.05) by 1.81-fold in the HSA group and by 2.02-fold in the TCC group. Abundance of C-X-C motif chemokine receptor 5 was increased (P< 0.05) by 1.74-fold in the HSA group and by 1.85-fold in the TCC group. POU class 2 associating factor 1 abundance was increased (P< 0.05) by 1.59-fold in the HSA group and by 1.83-fold in the TCC group. These genes have been associated with B cell functions that play roles in the tumor microenvironment and immune response by both preventing and promoting malignancies and may be indicators of cancer development. Additional validation and research of these identified genes is necessary to determine how nutritional support may affect their expression in dogs living with various cancer types.