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

Abstract

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.

Keywords: DR-70; biomarker; fibrinogen-fibrin degradation products; tumor detection.

FIGURE 1

Increased DR‐70 concentrations in the plasma of dogs with tumors. (A) The median concentrations of DR‐70 in healthy controls and dogs with neoplasms were 1.202 ± 0.610 and 2.130 ± 0.868 μg/mL, respectively. (B) ROC curve demonstrates the area under the ROC curve (AUC) for all dogs with tumors compared to healthy animals. The AUC is 0.883 under a 95% confidence interval of 0.842‐0.923, with a significant difference (P < .0001). Data were described as median ± interquartile range and analyzed by the Mann‐Whitney U test. P values <.05 were considered significant. ****P < .0001.

FIGURE 2

DR‐70 concentrations across multiple tumor types relative to the healthy cases. (A) DR‐70 concentrations were categorized by various common tumor types, such as lymphoma (n = 116), mast cell tumor (n = 17), melanoma (n = 12), TCC (n = 8), and mammary gland tumor (n = 5). (B) DR‐70 concentrations for lymphoma cases by immunophenotyping (B‐cell or T‐cell lymphoma). (C) DR‐70 concentrations for dogs with mast cell tumors according to grades (T0‐T1 or T2‐T4). (D) DR‐70 concentrations for melanoma cases by location (cutaneous or oral region). Data were described as median ± interquartile range and analyzed by the Mann‐Whitney U or Kruskal‐Wallis test. P values <.05 were considered to indicate statistical significance. *P < .05; **P < .01; ***P < .001; ****P < .0001; n.s., no significant difference.

FIGURE 3

Comparisons of DR‐70 concentrations in dogs with tumors by sex, age, and breeds. DR‐70 concentrations for dogs with tumors were not significantly different according to (A) sex (females or males), (B) age (< or >7 years old), and (C) breeds (large, medium, small, or toy breeds). Data were described as median ± interquartile range and analyzed by the Mann‐Whitney U or Kruskal‐Wallis test. P values <.05 were considered significant. n.s., no significant; §, no significant difference among the 5 groups.

FIGURE 4

Comparisons of DR‐70 concentrations in dogs with tumors and with nonneoplastic diseases. (A) Statistical analysis of DR‐70 concentrations stratified by nonneoplastic diseases, (B) inflammatory status, (C) and disease progression compared with healthy and tumor dogs. Data were described as median ± interquartile range and analyzed by the Kruskal‐Wallis test. P values <.05 were considered significant. n.s., no significant difference; *P < .05; ***P < .001; ****P < .0001. AD, acute diseases; CD, chronic diseases; HD, healthy dogs; ID, inflammatory diseases; N‐ID, non‐inflammatory diseases; N‐TD, non‐tumor dogs; TD, tumor dogs.