Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Vet Comp Oncol. 2021 Mar;19(1):172-182. doi: 10.1111/vco.12657. Epub 2020 Oct 19.
Canine mammary tumours (CMTs) are the most prevalent neoplasms in female dogs. Despite the high incidence of such tumours, a lack of easily accessible biomarkers still impedes early diagnosis of malignant CMTs. Herein we identify thymidylate synthetase (TYMS), hyaluronan and proteoglycan link protein 1 (HAPLN1) and insulin-like growth factor-binding protein 5 (IGFBP5) as CMT antigens eliciting corresponding autoantibodies in CMT cases. We establish enzyme-linked immunosorbent assays (ELISAs) to detect autoantibodies to TYMS (TYMS-AAb), HAPLN1 (HAPLN1-AAb) and IGFBP5 (IGFBP5-AAb) in sera from 81 dogs with malignant CMTs (41 in Stage I), 24 with benign CMTs and 35 healthy controls. Levels of all the three autoantibodies are elevated in the malignant group compared with the healthy or the benign group; notably, the elevated autoantibody levels significantly correlate with the stage-I CMTs. For discriminating malignant CMTs from healthy control, the area under curve (AUC) of TYMS-AAb is 0.694 with specificity of 82.9% and sensitivity of 50.6%. The AUC of utilising HAPLN1-AAb for distinguishing the stage-I CMTs from healthy controls is 0.711 with specificity of 77.1% and sensitivity of 58.5%. In differentiating malignant CMTs from the benign, the AUC of IGFBP5-AAb reaches 0.696 with specificity of 70.8% and sensitivity of 67.9%, and a combination of IGFBP5-AAb and TYMS-AAb increases the AUC to 0.72. Finally, the AUC of combined HAPLN1-AAb and IGFBP5-AAb in discriminating the stage-I CMTs from the benign achieves 0.731. Collectively, this study highlights a significant association of the three serum autoantibodies with early stage malignant CMTs.
犬乳腺肿瘤（CMTs）是雌性犬中最常见的肿瘤。尽管此类肿瘤的发病率很高，但缺乏易于获得的生物标志物仍然阻碍了恶性 CMT 的早期诊断。在此，我们鉴定胸苷酸合成酶（TYMS）、透明质酸和蛋白聚糖连接蛋白 1（HAPLN1）和胰岛素样生长因子结合蛋白 5（IGFBP5）作为 CMT 抗原，在 CMT 病例中引发相应的自身抗体。我们建立酶联免疫吸附试验（ELISA）来检测来自 81 只患有恶性 CMT（41 只处于 I 期）、24 只良性 CMT 和 35 只健康对照的血清中的针对 TYMS（TYMS-AAb）、HAPLN1（HAPLN1-AAb）和 IGFBP5（IGFBP5-AAb）的自身抗体。与健康或良性组相比，所有三种自身抗体的水平在恶性组中均升高；值得注意的是，升高的自身抗体水平与 I 期 CMT 显著相关。为了将恶性 CMT 与健康对照组区分开来，TYMS-AAb 的曲线下面积（AUC）为 0.694，特异性为 82.9%，灵敏度为 50.6%。利用 HAPLN1-AAb 区分 I 期 CMT 与健康对照的 AUC 为 0.711，特异性为 77.1%，灵敏度为 58.5%。在区分恶性 CMT 与良性时，IGFBP5-AAb 的 AUC 达到 0.696，特异性为 70.8%，灵敏度为 67.9%，而 IGFBP5-AAb 和 TYMS-AAb 的组合可将 AUC 提高到 0.72。最后，联合 HAPLN1-AAb 和 IGFBP5-AAb 区分 I 期 CMT 与良性的 AUC 达到 0.731。总的来说，这项研究强调了这三种血清自身抗体与早期恶性 CMT 之间的显著关联。
