Serglycin as a potential diagnostic biomarker for hemangiosarcoma in dogs

Abstract: Hemangiosarcoma (HSA) is a common splenic malignant neoplasia in dogs, originating from the endothelium. The tumor has an aggressive character, and the clinical symptoms of HSA are mostly due to the secondary effects of the tumor such as tumor growth or rupture. The prognosis is poor for HSA, usually with a survival time of under one year. It is challenging to distinguish HSA from benign neoplasias in the spleen, such as hematoma, which has a significantly better prognosis. Hence, many dogs are euthanized today due to suspicion of splenic HSA. With better diagnostic methods, several of these dogs could be cured as the tentative diagnosis may not be correct. Biomarkers have been discussed as a diagnostic method for HSA. As of today, few biomarkers have been evaluated and somewhat successfully implemented as a diagnostic method in the clinic. Serglycin is a proteoglycan that is mainly expressed by immune cells and have shown, in humans, a correlation between increased expression and malignant cancers. Hence, a quantification of serglycin in tumor canine patients could thus indicate tumor malignancy and be used for diagnostic purposes. In this study, serglycin expression was analyzed in splenic HSA tissue and non-pathological splenic tissue from formalin-fixed and paraffin-embedded material from dogs. Another gene, Eukaryotic elongation factor 2 (EEF2), was also included in the study to be compared with the expression of serglycin. The analysis was performed in real time with quantitative polymerase chain reaction (qPCR), where the expression in the tumor samples were compared with the healthy samples. Even though the quality of the qPCR results from the samples varied, this thesis still shows that there are trends that are interesting to continue to investigate with other methods and a larger patient material as a basis. Based on the samples showing the correct expression, this study support that splenic HSA tissue expresses significantly higher levels of serglycin than the non-pathological splenic tissue. This was not the case for EEF2, suggesting that serglycin is a more suitable biomarker for HSA than EEF2. However, before serglycin can be used as a biomarker at the clinic, more samples need to be analyzed to map out the normal variation in dogs. Also, as HSA was now compared with healthy spleens, it would be valuable to compare splenic HSA with other benign splenic masses as well. Lastly, a simple and inexpensive way of measuring the serglycin expression needs to be developed.