The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors

Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated...

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Main Authors: Stephen Hsien-Chi Yuan, Shih-Chieh Chang, Pei-Yi Chou, Youngsen Yang, Hao-Ping Liu
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/12/18/2463
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author Stephen Hsien-Chi Yuan
Shih-Chieh Chang
Pei-Yi Chou
Youngsen Yang
Hao-Ping Liu
author_facet Stephen Hsien-Chi Yuan
Shih-Chieh Chang
Pei-Yi Chou
Youngsen Yang
Hao-Ping Liu
author_sort Stephen Hsien-Chi Yuan
collection DOAJ
description Canine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated autoantibodies against thymidylate synthetase (TYMS), insulin-like growth factor-binding protein 5 (IGFBP5), hyaluronan and proteoglycan link protein 1 (HAPLN1), and anterior gradient 2 (AGR2), i.e., TYMS-AAb, IGFBP5-AAb, HAPLN1-AAb, and AGR2-AAb, respectively, by conducting serological enzyme-linked immunosorbent assays (ELISA). Herein we assessed serum AAb levels in 11 MMT dogs before and after surgery, demonstrating that IGFBP5-AAb and HAPLN1-AAb significantly decrease at 3- and 12-months post-surgery (<i>p</i> < 0.05). We evaluated the correlation between the presurgical AAb level and overall survival (OS) of 90 CMT dogs after surgery. Kaplan-Meier survival analysis reveals that IGFBP5-AAb<sup>HIgh</sup> and TYMS-AAb<sup>High</sup> are significantly correlated with worse OS (<i>p</i> = 0.017 and <i>p</i> = 0.029, respectively), while AGR2-AAb<sup>Low</sup> is correlated with somewhat poorer OS (<i>p</i> = 0.086). Areas under a time-dependent receiver operating characteristic curve (AUC) of IGFBP5-AAb and TYMS-AAb in predicting OS of MMT dogs are 0.611 and 0.616, respectively. Notably, MMT dogs presenting TYMS-AAb<sup>High</sup>/IGFBP5-AAb<sup>High</sup>/AGR2-AAb<sup>Low</sup> have worst OS (<i>p</i> = 0.0004). This study reveals an association between the serum AAb level and CMT prognosis.
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spelling doaj.art-b439fed6b1204d86aceeedae99ab034f2023-11-23T14:43:20ZengMDPI AGAnimals2076-26152022-09-011218246310.3390/ani12182463The Implication of Serum Autoantibodies in Prognosis of Canine Mammary TumorsStephen Hsien-Chi Yuan0Shih-Chieh Chang1Pei-Yi Chou2Youngsen Yang3Hao-Ping Liu4Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, TaiwanDivision of Hematology-Oncology, Department of Internal Medicine, Taichung, Veterans General Hospital, Taichung 40705, TaiwanDepartment of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 40227, TaiwanCanine mammary tumor (CMT) is the most prevalent neoplasm in female dogs. Tumor recurrence and metastasis occur in malignant CMT (MMT) dogs after surgery. Identification of serum prognostic biomarkers holds the potential to facilitate prediction of disease outcomes. We have identified CMT-associated autoantibodies against thymidylate synthetase (TYMS), insulin-like growth factor-binding protein 5 (IGFBP5), hyaluronan and proteoglycan link protein 1 (HAPLN1), and anterior gradient 2 (AGR2), i.e., TYMS-AAb, IGFBP5-AAb, HAPLN1-AAb, and AGR2-AAb, respectively, by conducting serological enzyme-linked immunosorbent assays (ELISA). Herein we assessed serum AAb levels in 11 MMT dogs before and after surgery, demonstrating that IGFBP5-AAb and HAPLN1-AAb significantly decrease at 3- and 12-months post-surgery (<i>p</i> < 0.05). We evaluated the correlation between the presurgical AAb level and overall survival (OS) of 90 CMT dogs after surgery. Kaplan-Meier survival analysis reveals that IGFBP5-AAb<sup>HIgh</sup> and TYMS-AAb<sup>High</sup> are significantly correlated with worse OS (<i>p</i> = 0.017 and <i>p</i> = 0.029, respectively), while AGR2-AAb<sup>Low</sup> is correlated with somewhat poorer OS (<i>p</i> = 0.086). Areas under a time-dependent receiver operating characteristic curve (AUC) of IGFBP5-AAb and TYMS-AAb in predicting OS of MMT dogs are 0.611 and 0.616, respectively. Notably, MMT dogs presenting TYMS-AAb<sup>High</sup>/IGFBP5-AAb<sup>High</sup>/AGR2-AAb<sup>Low</sup> have worst OS (<i>p</i> = 0.0004). This study reveals an association between the serum AAb level and CMT prognosis.https://www.mdpi.com/2076-2615/12/18/2463caninemammary tumorautoantibodyserumprognosissurvival
spellingShingle Stephen Hsien-Chi Yuan
Shih-Chieh Chang
Pei-Yi Chou
Youngsen Yang
Hao-Ping Liu
The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
Animals
canine
mammary tumor
autoantibody
serum
prognosis
survival
title The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
title_full The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
title_fullStr The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
title_full_unstemmed The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
title_short The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors
title_sort implication of serum autoantibodies in prognosis of canine mammary tumors
topic canine
mammary tumor
autoantibody
serum
prognosis
survival
url https://www.mdpi.com/2076-2615/12/18/2463
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