Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.
Department of Veterinary Surgery, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
PLoS One. 2022 Jun 6;17(6):e0265248. doi: 10.1371/journal.pone.0265248. eCollection 2022.
Since the discovery of klotho as an anti-aging gene, its association with tumors has been studied. Several previous studies have reported the down-expression of klotho in various human cancers, and much of its mechanism has been revealed. Nonetheless, the significance of klotho in canine mammary gland tumors is not yet known. This study aimed to determine whether klotho is expressed within normal canine mammary glands and whether the expression changes in benign and malignant tumors. Using immunohistochemistry, the experiment was conducted on eight normal canine mammary gland tissues and 55 mammary gland tumor samples. Additionally, the correlation between the Ki-67 proliferation index and clinicopathological features, such as age, tumor size, tumor grade, histologic type, and metastasis, was evaluated. All eight normal mammary gland tissues showed immunohistochemistry expression of klotho, and the expression significantly decreased as malignancy increased. Among the samples, 11% (3/28) of benign tumors and 26% (7/27) of malignant tumors showed negative klotho expression. Furthermore, higher Ki-67 expression, higher grades, and metastasis were confirmed to be associated with the negative klotho expression. Analysis of the survival curve for dogs with malignant tumors revealed that negative klotho expression was significantly associated with poor overall survival and disease-free survival. These results indicate that klotho is expressed in normal canine mammary glands and that negative klotho expression in canine mammary gland tumors is positively correlated with poor prognosis.
自从 klotho 被发现作为一种抗衰老基因以来，其与肿瘤的关联就一直受到研究。以前有几项研究报告称，klotho 在各种人类癌症中表达下调，其大部分机制已经被揭示。然而，klotho 在犬乳腺肿瘤中的意义尚不清楚。本研究旨在确定 klotho 是否在正常犬乳腺中表达，以及在良性和恶性肿瘤中表达是否发生变化。本实验采用免疫组织化学方法，对 8 例正常犬乳腺组织和 55 例乳腺肿瘤样本进行了检测。此外，还评估了 Ki-67 增殖指数与年龄、肿瘤大小、肿瘤分级、组织学类型和转移等临床病理特征之间的相关性。所有 8 例正常乳腺组织均显示 klotho 的免疫组织化学表达，随着恶性程度的增加，表达显著降低。在这些样本中，11%（3/28）的良性肿瘤和 26%（7/27）的恶性肿瘤显示 klotho 表达阴性。此外，较高的 Ki-67 表达、较高的分级和转移被证实与 klotho 表达阴性相关。对患有恶性肿瘤的犬的生存曲线分析表明，klotho 表达阴性与总体生存和无病生存不良显著相关。这些结果表明，klotho 在正常犬乳腺中表达，犬乳腺肿瘤中 klotho 表达阴性与预后不良呈正相关。
