Background <p>Canine mammary tumours (CMTs) represent a valuable spontaneous model for human breast cancer, as both share comparable pathological features and frequent alterations in the TP53 pathway. Although TP53 involvement in tumour development is well established, the diagnostic relevance of circulating TP53 autoantibodies in dogs remains insufficiently characterized. This study evaluated the diagnostic utility of TP53 autoantibodies in CMTs using a recombinant TP53-based immunoassay, supported by comparative analyses in human and experimental animal models.</p> Methods and Results <p>Recombinant canine TP53 protein was expressed and employed in indirect ELISA and dot blot assays to detect serum TP53 autoantibodies in 141 canine serum samples, including sera from dogs with mammary tumours and healthy controls. Comparative evaluation included serum samples from 100 human subjects (50 breast cancer patients and 50 healthy individuals) as well as a longitudinal N-nitroso-N-methylurea (NMU)–induced rat mammary tumour model to examine the temporal appearance of autoantibodies before and during tumour development.TP53 autoantibodies were detected in 60.0% of dogs with mammary tumours and were absent in healthy controls (<i>p</i> &lt; 0.0001), demonstrating high diagnostic accuracy (AUC 0.9587; sensitivity 60%; specificity 100%). Comparable trends were observed in human breast cancer sera (AUC 0.8956; sensitivity 52%; specificity 98%). Notably, longitudinal analysis of the NMU-induced rat model revealed the presence of TP53 autoantibodies before overt tumour formation, highlighting their potential role in early cancer detection.</p> Conclusions <p>These findings support recombinant TP53-based ELISA as a sensitive, specific, &amp; non-invasive diagnostic approach and identify circulating TP53 autoantibodies as promising early biomarkers in comparative and translational oncology.</p> Graphical abstract <p></p>

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Serum TP53 autoantibodies as a non-invasive diagnostic biomarker for canine mammary tumours: comparative insights from human and experimental rat model

  • Pradeep Kumar,
  • Sonal Saxena,
  • Sameer Shrivastava,
  • Owais Khan,
  • Rajeshwar Khandare,
  • Partha Pratim Borah,
  • Sabapathi Nagappan,
  • R. V. Purushotham,
  • M. Saminathan,
  • Abhinav Kumar

摘要

Background

Canine mammary tumours (CMTs) represent a valuable spontaneous model for human breast cancer, as both share comparable pathological features and frequent alterations in the TP53 pathway. Although TP53 involvement in tumour development is well established, the diagnostic relevance of circulating TP53 autoantibodies in dogs remains insufficiently characterized. This study evaluated the diagnostic utility of TP53 autoantibodies in CMTs using a recombinant TP53-based immunoassay, supported by comparative analyses in human and experimental animal models.

Methods and Results

Recombinant canine TP53 protein was expressed and employed in indirect ELISA and dot blot assays to detect serum TP53 autoantibodies in 141 canine serum samples, including sera from dogs with mammary tumours and healthy controls. Comparative evaluation included serum samples from 100 human subjects (50 breast cancer patients and 50 healthy individuals) as well as a longitudinal N-nitroso-N-methylurea (NMU)–induced rat mammary tumour model to examine the temporal appearance of autoantibodies before and during tumour development.TP53 autoantibodies were detected in 60.0% of dogs with mammary tumours and were absent in healthy controls (p < 0.0001), demonstrating high diagnostic accuracy (AUC 0.9587; sensitivity 60%; specificity 100%). Comparable trends were observed in human breast cancer sera (AUC 0.8956; sensitivity 52%; specificity 98%). Notably, longitudinal analysis of the NMU-induced rat model revealed the presence of TP53 autoantibodies before overt tumour formation, highlighting their potential role in early cancer detection.

Conclusions

These findings support recombinant TP53-based ELISA as a sensitive, specific, & non-invasive diagnostic approach and identify circulating TP53 autoantibodies as promising early biomarkers in comparative and translational oncology.

Graphical abstract