# Machine learning-assisted detection of canine mammary tumors using serum autoantibody signatures

**Authors:** Bluest Lan, Chia-Yu Chang, Shin-Wu Liu, Chih-Ching Wu, Kuan-Ming Lai, Hao-Ping Liu

PMC · DOI: 10.1080/01652176.2026.2617470 · The Veterinary Quarterly · 2026-01-21

## TL;DR

This study uses machine learning and blood autoantibodies to detect canine mammary tumors noninvasively, showing promising early results.

## Contribution

A novel noninvasive diagnostic model for canine mammary tumors using autoantibody signatures and machine learning is developed.

## Key findings

- A machine learning model achieved 75.3% sensitivity and 74.4% specificity for overall CMT detection.
- The model showed 92.7% sensitivity for malignant tumors but lower specificity (61.5%).
- Positive and negative predictive values were 0.74–0.75 and 0.75–0.91, respectively, assuming a 0.5 prevalence.

## Abstract

Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs, yet early detection remains challenging due to the lack of clinically validated, noninvasive biomarkers. This study aimed to develop a noninvasive diagnostic model for CMT detection by integrating serum autoantibody biomarkers with machine learning. Serum samples from 154 dogs with mammary tumors (31 benign, 123 malignant) and 39 healthy controls were analyzed using a custom multiplex immunoassay detecting autoantibodies against AGR2, HAPLN1, IGFBP5, and TYMS, normalized to anti-BSA levels. Median fluorescence intensity (MFI), standardized autoantibody ratios, and their combination, together with clinical variables, were used to train random forest classifiers. The model based on standardized autoantibody ratios achieved the best performance, with an AUC of 0.79 (sensitivity 75.3%, specificity 74.4%) for overall CMT detection; 0.78 (92.7%, 61.5%) for malignant CMTs; and 0.77 (82.2%, 71.8%) for early-stagemalignancies. Assuming a CMT prevalence of 0.5 in the hospital-referred population, the positive and negative predictive values ranged from 0.74–0.75 and 0.75–0.91, respectively. This proof-of-concept study demonstrates that a machine learning-assisted multiplex autoantibody assay offers a feasible noninvasive approach for CMT detection. Further validation in larger, independent cohorts is warranted to support clinical translation in veterinary oncology.

## Linked entities

- **Genes:** AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551], HAPLN1 (hyaluronan and proteoglycan link protein 1) [NCBI Gene 1404], IGFBP5 (insulin like growth factor binding protein 5) [NCBI Gene 3488], TYMS (thymidylate synthetase) [NCBI Gene 7298]

## Full-text entities

- **Genes:** TK1 (thymidine kinase 1) [NCBI Gene 100855947], AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 482333], HAPLN1 (hyaluronan and proteoglycan link protein 1) [NCBI Gene 488921], CRP (C-reactive protein) [NCBI Gene 488629], IGFBP5 (insulin like growth factor binding protein 5) [NCBI Gene 610316], ALB (albumin) [NCBI Gene 403550] {aka CSA}, TK1 [NCBI Gene 483343], TYMS (thymidylate synthetase) [NCBI Gene 607417] {aka TS}
- **Diseases:** CMT (MESH:C537989), stage I (MESH:D062706), I (MESH:D006969), stage I-II malignant CMTs (MESH:D018198), I-II (MESH:D056829), Tumor (MESH:D009369), systemic disease (MESH:D034721), Canine mammary tumors (MESH:D015674)
- **Chemicals:** deoxythymidine monophosphate (MESH:D013938)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12825649/full.md

## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12825649/full.md

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Source: https://tomesphere.com/paper/PMC12825649