Heilmann Romy M, McNiel Elizabeth A, Grützner Niels, Lanerie David J, Suchodolski Jan S, Steiner Jörg M
College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 23, DE-04103, Leipzig, Germany.
Gastrointestinal Laboratory, Texas A&M University, TAMU 4474, College Station, TX, 77843-4474, USA.
BMC Vet Res. 2017 Apr 21;13(1):112. doi: 10.1186/s12917-017-1032-5.
Onset of canine transitional cell carcinoma (TCC) and prostatic carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of the disease. A biomarker that can facilitate early detection of TCC/PCA and improve patient survival would be useful. S100A8/A9 (calgranulin A/B or calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate immune system and are associated with several inflammatory disorders. S100A8/A9 is also expressed by epithelial cells after malignant transformation and is involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up-regulated in human PCA and TCC, whereas the results for S100A12 have been ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract disease, other neoplasms, or urinary tract infections, and 75 healthy controls (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species-specific radioimmunoassays and normalized against urine specific gravity [S100A8/A9; S100A12], urine creatinine concentration, and urine protein concentration and the uCalR were compared among the groups of dogs.
S100A8/A9 had the highest sensitivity (96%) and specificity (66%) to detect TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a urinary tract infection (sensitivity: 91%, specificity: 60%). Using a S100A8/A9 ≥ 109.9 to screen dogs ≥6 years of age for TCC/PCA yielded a negative predictive value of 100%.
S100A8/A9 and uCalR may have utility for diagnosing TCC/PCA in dogs, and S100A8/A9 may be a good screening test for canine TCC/PCA.
犬移行细胞癌(TCC)和前列腺癌(PCA)通常起病隐匿,犬只就诊时往往已处于疾病晚期。一种能够促进TCC/PCA早期检测并提高患者生存率的生物标志物将很有用。S100A8/A9(钙粒蛋白A/B或钙卫蛋白)和S100A12(钙粒蛋白C)由先天免疫系统的细胞表达,并与多种炎症性疾病相关。S100A8/A9在恶性转化后的上皮细胞中也有表达,并参与细胞增殖和转移的调控。S100A8/A9在人类PCA和TCC中上调,而S100A12的结果尚不明确。此外,尿S100A8/A9与S100A12的比值(uCalR)可能有潜力作为犬TCC/PCA的标志物。本研究的目的是通过使用164只患有TCC/PCA、非肿瘤性泌尿系统疾病、其他肿瘤或泌尿系统感染的犬以及75只健康对照犬的数据和尿液样本(巢式病例对照研究),评估尿S100/钙粒蛋白检测犬TCC/PCA的诊断准确性。对各组犬的尿S100A8/A9和S100A12(通过物种特异性放射免疫测定法测量,并根据尿比重[S100A8/A9;S100A12]、尿肌酐浓度、尿蛋白浓度进行标准化)以及uCalR进行比较。
S100A8/A9检测TCC/PCA的敏感性最高(96%),特异性为66%,排除泌尿系统感染的犬后特异性达到75%。uCalR最能区分患有TCC/PCA的犬和患有泌尿系统感染的犬(敏感性:91%,特异性:60%)。使用S100A8/A9≥109.9对6岁及以上犬进行TCC/PCA筛查,阴性预测值为100%。
S100A8/A9和uCalR可能对诊断犬TCC/PCA有用,且S100A8/A9可能是犬TCC/PCA的一种良好筛查试验。