Marques Cláudia S, Soares Maria, Santos Ana, Correia Jorge, Ferreira Fernando
Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal.
Oncotarget. 2017 Nov 11;8(62):105775-105789. doi: 10.18632/oncotarget.22398. eCollection 2017 Dec 1.
The feline mammary carcinoma (FMC) is the third most common tumor in cat, sharing many clinicopathological features with human breast cancer and thus, considered a suitable model for comparative oncology. Due to its poor prognosis, further studies are required to improve the diagnostic accuracy and treatment of cats with spontaneous mammary carcinoma. Recently, it was reported that the overexpression of stromal cell-derived factor-1 (SDF-1) has great value in human breast cancer diagnosis, suggesting that diagnostic tools and therapies targeting the SDF-1 ligand can improve the clinical outcome. In this study, we aimed to evaluate if serum SDF-1 levels can also be used as a biomarker of mammary carcinoma in cats and to analyze if serum SDF-1 levels are associated with clinicopathological features, linked to a specific FMC subtype or correlated with the tumor expression of SDF-1 receptor, the chemokine C-X-C motif receptor 4 (CXCR4). Results showed that cats with mammary carcinoma had significantly higher serum SDF-1 levels than healthy controls (=0.035) and ROC analysis revealed that the best cut-off value to differentiate sick from healthy animals was 2 ng/ml (specificity: 80%; sensitivity: 57%; AUC=0.715). Significant associations were also found between cats with elevated serum SDF-1 concentrations (≥ 2 ng/ml) and HER2-overexpressing mammary carcinomas (Luminal B-like and HER2-positive subtypes, <0.0001), CXCR4-negative mammary carcinomas (=0.027), mammary carcinomas with small size (<3 cm, =0.027) and tumors with low Ki-67 expression (=0.012). No statistical associations were found between serum SDF-1 levels and overall or disease-free survival. In summary, our results show that serum SDF-1 levels can be used as a biomarker of feline mammary carcinoma, especially in cats with HER2-overexpressing mammary tumors. Data suggest that targeted therapies against the SDF-1 ligand and/or its CXC4 receptor may be effective for the treatment of FMC, as described for human breast cancer, strengthening the concept that spontaneous feline mammary carcinoma is a suitable model for comparative oncology.
猫乳腺肿瘤（FMC）是猫类中第三常见的肿瘤，与人类乳腺癌具有许多临床病理特征，因此被认为是比较肿瘤学的合适模型。由于其预后较差，需要进一步研究以提高对自发性乳腺肿瘤猫的诊断准确性和治疗效果。最近有报道称，基质细胞衍生因子-1（SDF-1）的过表达在人类乳腺癌诊断中具有重要价值，这表明针对SDF-1配体的诊断工具和治疗方法可以改善临床结果。在本研究中，我们旨在评估血清SDF-1水平是否也可作为猫乳腺肿瘤的生物标志物，并分析血清SDF-1水平是否与临床病理特征相关，是否与特定的FMC亚型有关，或与SDF-1受体（趋化因子C-X-C基序受体4，CXCR4）的肿瘤表达相关。结果显示，患有乳腺肿瘤的猫血清SDF-1水平显著高于健康对照组（=0.035），ROC分析表明，区分患病动物与健康动物的最佳临界值为2 ng/ml（特异性：80%；敏感性：57%；AUC=0.715）。血清SDF-1浓度升高（≥2 ng/ml）的猫与HER2过表达的乳腺肿瘤（Luminal B样和HER2阳性亚型，<0.0001）、CXCR4阴性的乳腺肿瘤（=0.027）、小尺寸乳腺肿瘤（<3 cm，=0.027）以及Ki-67低表达肿瘤（=0.012）之间也存在显著关联。血清SDF-1水平与总生存期或无病生存期之间未发现统计学关联。总之，我们的结果表明，血清SDF-1水平可作为猫乳腺肿瘤的生物标志物，特别是在HER2过表达乳腺肿瘤的猫中。数据表明，针对SDF-1配体和/或其CXC4受体的靶向治疗可能对FMC治疗有效，正如在人类乳腺癌中所描述的那样，强化了自发性猫乳腺肿瘤是比较肿瘤学合适模型的概念。
