Overexpression of Kynurenine 3-Monooxygenase Correlates with Cancer Malignancy and Predicts Poor Prognosis in Canine Mammary Gland Tumors.

Tumor biomarkers are developed to indicate tumor status, clinical outcome, or prognosis. Since currently there are no effective biomarkers for canine mammary tumor (CMT), this study intended to verify whether kynurenine 3-monooxygenase (KMO), one of the key enzymes involved in tryptophan catabolism, is competent for predicting prognosis in patients with CMT. By investigating a series of 86 CMT clinical cases, we found that both gene and protein expression of KMO discriminated malignant from benign CMTs and was significantly higher in stage IV and V tumors than in lower-stage CMTs. About 73.7% of malignant CMTs showed strong expression of KMO which correlated with lower overall survival rates in patients. Further, downregulation of KMO activity significantly inhibited cell proliferation of CMT cells. Taken together, the findings indicated that KMO is a potential biomarker for tumor diagnosis, and this might open up new perspectives for clinical applications of CMT.

Gene-expression profiling to identify genes related to spontaneous tumor regression in a canine cancer model.

Microarray transcriptome study in cancer has been commonly used to investigate tumorigenic mechanisms. The unique growth pattern of spontaneous regression (SR) after progressive (P) growth in canine transmissible venereal tumor (CTVT) provides a valuable cancer model to study the genome-wide differences in samples between the two stages of growth. In this study, Affymetrix analysis was performed based on the canine genome to compare the gene expression profiles of CTVT P- and SR-phase tumors. A total of 459 (278 up-regulated and 181 down-regulated) genes were identified as being differentially-expressed during the SR phase by the 2-fold method. Further analysis of these genes revealed that the expression of three genes associated with IL-6 production -TIMD-4, GPNMB and PLTP - was significantly higher in SR-phase tumors than in P-phase tumors; these results were also confirmed by real time RT-PCR in tumor tissues of beagles. In addition, we found that Th17-related genes were over-expressed in the SR phase, suggesting autoimmune responses involvement in tumor regression. Although the interaction between CTVT and host immunity were partially investigated in previous studies, our results enable us to gain new insight into the genes and possible mechanisms involved in tumor regression and reveal potentially useful targets for cancer therapy.