Down-expression of klotho in canine mammary gland tumors and its prognostic significance

© 2022 Chung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.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.N

MicroRNA and Messenger RNA Expression Profiles in Canine Mammary Gland Tumor

Canine mammary gland tumor (CMT) is the most frequently diagnosed neoplasm in intact female dogs. As prognosis depends on the malignancy of tumors and metastasis levels, early and accurate diagnosis are crucial for prolongation of life expectancy. The genetic similarity of dogs with humans in addition to environmental and physiological similarities make them ideal models for the study of cancer. In this study, we analyzed differentially expressed microRNAs followed by RNA-Seq to investigate the alterations in mRNA levels based on the malignancy (benign, malignant) and the biopsy locations (tumors, surrounding normal tissues). We identified multiple breast cancer-related genes regardless of malignancy. We found cfa-miR-503 to be the only miRNA that showed altered expression in response to malignancy in CMTs. Although further validation is needed, cfa-miR-503 could be used as a potential diagnostic biomarker as well as a potential RNA-based anti-tumor drug in malignant CMTs