DR-70 (fibrinogen-fibrin degradation products) as a prognostic biomarker in dogs with neoplasms.

Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

Increased plasma DR-70 (fibrinogen-fibrin degradation products) concentrations as a diagnostic biomarker in dogs with neoplasms.

BACKGROUND: Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for fibrinogen and fibrin degradation products (DR-70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR-70 for veterinary medicine however has yet to be determined. OBJECTIVES: Investigate the diagnostic value of DR-70 concentrations by comparing them between healthy dogs and dogs with tumors. ANIMALS: Two hundred sixty-three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison. METHODS: The DR-70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests. RESULTS: The median concentration of DR-70 was 2.130 ± 0.868 µg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 µg/mL; P < .0001). With a cut-off of 1.514 µg/mL, the sensitivity and specificity of DR-70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR-70 concentration can be an effective tumor biomarker in veterinary medicine. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DR-70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR-70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR-70 as a tumor biomarker.

The High Expression of Legumain in Canine Neoplasms: A Retrospective Analysis of 100 Cases.

Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively (p < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study.