Di Benedetto, A, Mottolese, M, Sperati, F et al. (12 more authors) (2017) Association between AXL, Hippo transducers and survival outcomes in male breast cancer. Journal of Cellular Physiology, 232 (8). pp. 2246-2252. ISSN 0021-9541
Abstract
Male breast cancer (MBC) is an uncommon malignancy. We have previously reported that the expression of the Hippo transducers TAZ/YAP and their target CTGF was associated with inferior survival in MBC patients. Preclinical evidence demonstrated that Axl is a transcriptional target of TAZ/YAP. Thus, we herein assessed AXL expression to further investigate the significance of active TAZ/YAP-driven transcription in MBC. For this study, 255 MBC samples represented in tissue microarrays were screened for AXL expression, and 116 patients were included. The association between categorical variables was verified by the Pearson’s Chi-squared test of independence (2-tailed) or the Fisher Exact test. The relationship between continuous variables was tested with the Pearson's correlation coefficient. The Kaplan-Meier method was used for estimating survival curves, which were compared by log-rank test. Factors potentially impacting 10-year and overall survival were verified in Cox proportional regression models. AXL was positively associated with the TAZ/CTGF and YAP/CTGF phenotypes (p=0.001 and p=0.002, respectively). Patients with TAZ/CTGF/AXL- or YAP/CTGF/AXL-expressing tumors had inferior survival compared with non-triple-positive patients (log rank p=0.042 and p=0.048, respectively). The variables TAZ/CTGF/AXL and YAP/CTGF/AXL were adverse factors for 10-year survival in the multivariate Cox models (HR 2.31, 95%CI:1.02-5.22, p=0.045, and HR 2.27, 95%CI:1.00-5.13, p=0.050). Nearly comparable results were obtained from multivariate analyses of overall survival. The expression pattern of AXL corroborates the idea of the detrimental role of TAZ/YAP activation in MBC. Overall, Hippo-linked biomarkers deserve increased attention in this rare disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, Wiley. This is the peer reviewed version of the following article: 'Di Benedetto, A, Mottolese, M, Sperati, F et al (2017) Association between AXL, Hippo transducers and survival outcomes in male breast cancer. Journal of Cellular Physiology, 232 (8). pp. 2246-2252', which has been published in final form at https://doi.org/10.1002/jcp.25745. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | Male Breast Cancer; AXL; TAZ; YAP; Hippo Pathway |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L378 Expired: Use BreastCancerNow 605321 NOT GIVEN |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Dec 2016 14:43 |
Last Modified: | 18 Dec 2017 01:38 |
Published Version: | https://doi.org/10.1002/jcp.25745 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/jcp.25745 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:109623 |