The expression of histone lysine demethylase 2B in canine hemangiosarcoma is associated with disease progression

Abstract

Canine hemangiosarcoma (HSA), a highly fatal mesenchymal tumour of dogs, originates from the endothelial cells lining of blood vessels. It is characterized by a short survival time with a mean survival time of only 4 months. Recently, we showed that histone lysine demethylase 2B (KDM2B) was highly expressed in canine HSA and was important in HSA tumour cell survival by positively regulating DNA repair mechanisms. KDM2B has been reported to be related to disease progression and patient survival in several human cancers. Thus, in this study, we studied the relationship of KDM2B expression levels with several patient clinical profiles to investigate the role of KDM2B in clinical HSA tumours. We analysed 37 canine HSA cases and found that KDM2B is highly expressed in stage 3 HSA compared to stage 1 HSA. High KDM2B expression was also found in male dogs compared to female dogs. No correlation was observed between KDM2B expression and age. Classifying HSA patients into high and low KDM2B expression groups revealed that the high KDM2B group showed shorter overall survival than the low KDM2B group. Based on these results, we suggest that KDM2B expression is associated with disease progression in HSA.

New molecular targets in canine hemangiosarcoma—Comparative review and future of the precision medicine

“…234 Expression level of KDM2B is highly dependent on the stage of the disease, with the highest percentage of expression in stage III (in comparison with stage I), and positively correlates with shortening of OST. 235 As proven in laboratory conditions, it might be a potentially targetable aberration due to the fact that GSK-J4, a histone demethylase inhibitor, induces apoptosis leading to cell death and also decreases tumour size. 234 In mouse derived HSA cells, Gulay et al 235 proved that macrophages are major constituents of the tumour microenvironment, 236 and HSA cells can independently induce M2 polarization and PD-L1 expression on them.…”

“…235 As proven in laboratory conditions, it might be a potentially targetable aberration due to the fact that GSK-J4, a histone demethylase inhibitor, induces apoptosis leading to cell death and also decreases tumour size. 234 In mouse derived HSA cells, Gulay et al 235 proved that macrophages are major constituents of the tumour microenvironment, 236 and HSA cells can independently induce M2 polarization and PD-L1 expression on them.…”

“…Silencing KDM2B in HSA cells results in increased cell death in vitro by inducing apoptosis through DNA damage accumulation 234 . Expression level of KDM2B is highly dependent on the stage of the disease, with the highest percentage of expression in stage III (in comparison with stage I), and positively correlates with shortening of OST 235 . As proven in laboratory conditions, it might be a potentially targetable aberration due to the fact that GSK‐J4, a histone demethylase inhibitor, induces apoptosis leading to cell death and also decreases tumour size 234 .…”