SDF-1: a new diagnostic serum marker of feline mammary carcinomas

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SDF-1: a new diagnostic serum marker of feline mammary carcinomas

Quarta, 24.01.2018

Feline mammary carcinoma (FMC) represents a good translational model for human breast cancer, based on similar clinical and pathological features. On the other hand, the chemokine SDF-1 and its receptor CXCR4 have been linked to invasion, metastasis and poor prognosis in human breast cancer. The CIISA team, coordinated by Prof. Fernando Ferreira (CIISA, Faculty of Veterinary Medicine, University of Lisbon) reported for the first time, a high prevalence of serum SDF-1 levels in cats with FMC, when compared to healthy ones. A cut-off value of 2 ng/ml was obtained, presenting SDF-1 as an accurate diagnostic tool to diagnose FMC. Moreover, CXCR4 was overexpressed in FMC tissue, as already reported for human breast cancer. This study also brings new evidence on an association between high serum SDF-1 levels and HER2-overexpressing FMC molecular subtypes. The authors concluded that SDF-1 can be an important diagnostic marker for FMC, and a potential drug target to treat cats with HER2-positive mammary carcinomas.

 

Authors and Affiliations:
Cláudia S. Marques, Maria Soares, Ana Santos, Jorge Correia e Fernando Ferreira
CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisbon, Portugal 

Abstract:
Serum SDF-1 levels are a reliable diagnostic marker of feline mammary carcinoma, discriminating HER2-overexpressing tumors from other subtypes. 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 (p=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, p<0.0001), CXCR4-negative mammary carcinomas (p=0.027), mammary carcinomas with small size (<3 cm, p=0.027) and tumors with low Ki-67 expression (p=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.

Journal: Oncotarget. 2017; 8:105775-105789

Linkhttps://doi.org/10.18632/oncotarget.22398