Gameiro Andreia, Nascimento Catarina, Urbano Ana Catarina, Correia Jorge, Ferreira Fernando
CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária da Universidade de Lisboa, Lisbon, Portugal.
Front Vet Sci. 2021 Feb 10;8:625147. doi: 10.3389/fvets.2021.625147. eCollection 2021.
Obesity is an established risk factor for breast cancer in post-menopausal women, being associated with elevated serum levels of leptin. Although overweight is a common condition in cat, the role of leptin and its receptor in feline mammary carcinoma remains unsettled. In this study, serum leptin and leptin receptor (ObR) levels were investigated in 58 cats with mammary carcinoma and compared with those of healthy animals, as were the expression levels of leptin and ObR in tumor tissues. The results showed that the Free Leptin Index is significantly decreased in cats with mammary carcinoma ( = 0.0006), particularly in those with luminal B and HER2-positive tumors, and that these animals also present significantly lower serum leptin levels ( < 0.0001 and < 0.005, respectively). Interestingly, ulcerating tumors ( = 0.0005) and shorter disease-free survival ( = 0.0217) were associated to serum leptin levels above 4.17 pg/mL. In contrast, elevated serum ObR levels were found in all cats with mammary carcinoma ( < 0.0001), with levels above 16.89 ng/mL being associated with smaller tumors ( = 0.0118), estrogen receptor negative status ( = 0.0291) and increased serum levels of CTLA-4 ( = 0.0056), TNF-α ( = 0.0025), PD-1 ( = 0.0023), and PD-L1 ( = 0.0002). In tumor samples, leptin is overexpressed in luminal B and triple-negative carcinomas ( = 0.0046), whereas ObR is found to be overexpressed in luminal B tumors ( = 0.0425). Altogether, our results support the hypothesis that serum levels of leptin and ObR can be used as biomarkers of specific feline mammary carcinoma subtypes, and suggests the use of leptin antagonists as a therapeutic tool, reinforcing the utility of the cat as a cancer model.
肥胖是绝经后女性患乳腺癌的一个既定风险因素，与血清瘦素水平升高有关。虽然超重在猫中是一种常见情况，但瘦素及其受体在猫乳腺癌中的作用仍未明确。在本研究中，对58只患有乳腺癌的猫的血清瘦素和瘦素受体（ObR）水平进行了研究，并与健康动物的水平进行了比较，同时也研究了肿瘤组织中瘦素和ObR的表达水平。结果显示，患有乳腺癌的猫的游离瘦素指数显著降低（P = 0.0006），特别是那些患有管腔B型和HER2阳性肿瘤的猫，并且这些动物的血清瘦素水平也显著较低（分别为P < 0.0001和P < 0.005）。有趣的是，溃疡型肿瘤（P = 0.0005）和较短的无病生存期（P = 0.0217）与血清瘦素水平高于4.17 pg/mL有关。相反，在所有患有乳腺癌的猫中均发现血清ObR水平升高（P < 0.0001），ObR水平高于16.89 ng/mL与较小的肿瘤（P = 0.0118）、雌激素受体阴性状态（P = 0.0291）以及血清CTLA-4（P = 0.0056）、TNF-α（P = 0.0025）、PD-1（P = 0.0023）和PD-L1（P = 0.0002）水平升高有关。在肿瘤样本中，瘦素在管腔B型和三阴性癌中过度表达（P = 0.0046），而ObR在管腔B型肿瘤中过度表达（P = 0.0425）。总之，我们的结果支持这样的假设，即血清瘦素和ObR水平可作为特定猫乳腺癌亚型的生物标志物，并建议使用瘦素拮抗剂作为一种治疗工具，这进一步证明了猫作为癌症模型的实用性。
