An enzyme that plays an important role in cell proliferation shows promise as a cancer biomarker in horses, researchers report.
Clinical signs of cancer are generally vague and unspecific in horses. They most commonly include apathy, weight loss, exercise intolerance and fever.
Liya Wang and her colleagues, writing in the journal BMC Molecular and Cell Biology, said systemic cancer should be considered as a possible diagnosis in such cases when more common causes, such as infectious diseases, severe parasite burdens or dental or digestive disorders, have been ruled out.
Cancer should also be suspected if horses do not respond to standard therapy and show progressive loss of function of one or more organ systems.
Blood and biochemical profile changes in equine cancers also tend to be nonspecific, but can include anaemia, an increase in blood neutrophils and elevated globulin concentrations.
Further diagnostic work-ups may be quite extensive and invasive, often requiring the expertise of a veterinary specialist. Depending on clinical signs, this work-up can include a rectal exam, an abdominal and thoracic ultrasound, chest x-rays, and biopsies from internal organs collected with ultrasound guidance or during an explorative laparotomy.
The researchers, with the Swedish University of Agricultural Sciences and the University of Bern, said the lack of reliable and noninvasive equine cancer biomarkers results in delayed diagnosis, ineffective treatment options, and poor overall survival.
The study team looked at the potential of thymidine kinase 1 (TK1) as a cancer biomarker in horses, in particular in equines with lymphoma.
TK1 is an enzyme that plays a key role in the synthesis of deoxythymidine triphosphate and is thus important for DNA replication and cell proliferation.
TK1 levels are highest during the phase of the cell cycle in which DNA is replicated, and rapidly degrades after cell division.
In cancer cells, TK1 is upregulated, resulting in a leakage of excess TK1 into the blood. Consequently, serum TK1 has been used as a diagnostic and prognostic cancer biomarker, mainly in human medicine.
The study team set out to characterize equine TK1 and to evaluate its suitability as a serum biomarker for equine lymphoma.
Serum TK1 activity was measured in samples collected from seven horses with confirmed lymphoma, five with suspected lymphoma, 107 control horses with non-tumour-related concurrent diseases, and 42 control horses without concurrent diseases.
Serum TK1 activity levels were significantly higher in horses with lymphoma and suspected lymphoma than the controls, including those with a diverse range of non-cancer-related diseases.
Levels were also elevated in this tumour-free group, but they were not as high as in the horses with cancer. TK1 levels were lower in the healthy control horses that had no concurrent diseases.
The difference in levels between the lymphoma group and the tumour-free group with diverse diseases was significant, the researchers reported.
The results indicate that serum TK1 could serve as a promising cancer biomarker in horses, they concluded.
Discussing their findings, the researchers noted that serum TK1 activity has been used as a biomarker for health screening to detect premalignant diseases and for cancer diagnosis and prognosis in human medicine.
In veterinary medicine, serum TK1 has also been shown to be a useful biomarker to diagnose malignant diseases in dogs and to monitor treatment.
“Since equine lymphoma is a disease with many faces and usually unspecific symptoms, a reliable blood-based biomarker such as TK1 would greatly assist in the noninvasive identification of horses with lymphoma in not only advanced but also early stages of cancer.
“Indeed, in this study, we were able to show that the serum TK1 activity in horses with confirmed lymphoma was significantly higher than the activities in control horses with and without concurrent diseases.”
They said their study included a relatively large and diverse group of control horses, including a population of old, well-monitored horses owned by a foundation, and thus offered a particularly adequate and reliable control group.
The prognosis of lymphoma depends on the type and extent of the cancer. In some forms, such as generalized, alimentary or mediastinal lymphoma, the prognosis is poor, particularly if the disease is diagnosed at advanced stages.
“Therefore, early diagnosis is vital for the success of treatment and thus overall survival,” they said.
“Future studies evaluating serum TK1 as a diagnostic and prognostic biomarker for equine neoplastic conditions in larger study cohorts are warranted.”
The authors said their laboratory work characterizing TK1 also serves as a starting point for the understanding of the basic molecular biology of this enzyme in horses and its diagnostic and therapeutic uses in equine cancer treatment.
The study team comprised Wang, Hanan Sharif, Staffan Eriksson and Henrik Rönnberg, all with the Swedish University of Agricultural Sciences; and Lucia Unger and Vinzenz Gerber with the University of Bern.
Wang, L., Unger, L., Sharif, H. et al. Molecular characterization of equine thymidine kinase 1 and preliminary evaluation of its suitability as a serum biomarker for equine lymphoma. BMC Mol and Cell Biol 22, 59 (2021). https://doi.org/10.1186/s12860-021-00399-x