Association between AXL, Hippo transducers and survival outcomes in male breast cancer

Male breast cancer (MBC) is an uncommon malignancy. We have previously reported\r\nthat the expression of the Hippo transducers TAZ/YAP and their target CTGF was\r\nassociated with inferior survival in MBC patients. Preclinical evidence\r\ndemonstrated that Axl is a transcriptional target of TAZ/YAP. Thus, we herein\r\nassessed AXL expression to further investigate the significance of active\r\nTAZ/YAP-driven transcription in MBC. For this study, 255 MBC samples represented \r\nin tissue microarrays were screened for AXL expression, and 116 patients were\r\nincluded. The association between categorical variables was verified by the\r\nPearson's Chi-squared test of independence (2-tailed) or the Fisher Exact test.\r\nThe relationship between continuous variables was tested with the Pearson's\r\ncorrelation coefficient. The Kaplan-Meier method was used for estimating survival\r\ncurves, which were compared by log-rank test. Factors potentially impacting\r\n10-year and overall survival were verified in Cox proportional regression models.\r\nAXL was positively associated with the TAZ/CTGF and YAP/CTGF phenotypes\r\n(p = 0.001 and p = 0.002, respectively). Patients with TAZ/CTGF/AXL- or\r\nYAP/CTGF/AXL-expressing tumors had inferior survival compared with\r\nnon-triple-positive patients (log rank p = 0.042 and p = 0.048, respectively).\r\nThe variables TAZ/CTGF/AXL and YAP/CTGF/AXL were adverse factors for 10-year\r\nsurvival in the multivariate Cox models (HR 2.31, 95%CI:1.02-5.22, p = 0.045, and\r\nHR 2.27, 95%CI:1.00-5.13, p = 0.050). Nearly comparable results were obtained\r\nfrom multivariate analyses of overall survival. The expression pattern of AXL\r\ncorroborates the idea of the detrimental role of TAZ/YAP activation in MBC.\r\nOverall, Hippo-linked biomarkers deserve increased attention in this rare\r\ndisease. This article is protected by copyright. All rights reserved.