TY - JOUR
T1 - Association between AXL, Hippo Transducers, and Survival Outcomes in Male Breast Cancer
AU - Di Benedetto, Anna
AU - Mottolese, Marcella
AU - Sperati, Francesca
AU - Ercolani, Cristiana
AU - Di Lauro, Luigi
AU - Pizzuti, Laura
AU - Vici, Patrizia
AU - Terrenato, Irene
AU - Shaaban, Abeer M.
AU - Humphries, Matthew P.
AU - Sundara-Rajan, Sreekumar
AU - Barba, Maddalena
AU - Speirs, Valerie
AU - De Maria Marchiano, Ruggero
AU - Maugeri-Saccà, Marcello
PY - 2017
Y1 - 2017
N2 - 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 KaplanâMeier 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:1.02â5.22, P = 0.045, and HR 2.27, 95%CI:1.00â5.13, 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. J. Cell. Physiol. 232: 2246â2252, 2017. © 2016 Wiley Periodicals, Inc.
AB - 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 KaplanâMeier 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:1.02â5.22, P = 0.045, and HR 2.27, 95%CI:1.00â5.13, 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. J. Cell. Physiol. 232: 2246â2252, 2017. © 2016 Wiley Periodicals, Inc.
KW - Adaptor Proteins
KW - Aged
KW - Biomarkers
KW - Breast Neoplasms
KW - Cell Biology
KW - Chi-Square Distribution
KW - Clinical Biochemistry
KW - Connective Tissue Growth Factor
KW - Humans
KW - Immunohistochemistry
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Phosphoproteins
KW - Physiology
KW - Predictive Value of Tests
KW - Prognosis
KW - Proportional Hazards Models
KW - Proto-Oncogene Proteins
KW - Receptor Protein-Tyrosine Kinases
KW - Retrospective Studies
KW - Risk Factors
KW - Signal Transducing
KW - Signal Transduction
KW - Time Factors
KW - Tissue Array Analysis
KW - Transcription Factors
KW - Tumor
KW - Adaptor Proteins
KW - Aged
KW - Biomarkers
KW - Breast Neoplasms
KW - Cell Biology
KW - Chi-Square Distribution
KW - Clinical Biochemistry
KW - Connective Tissue Growth Factor
KW - Humans
KW - Immunohistochemistry
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Multivariate Analysis
KW - Phosphoproteins
KW - Physiology
KW - Predictive Value of Tests
KW - Prognosis
KW - Proportional Hazards Models
KW - Proto-Oncogene Proteins
KW - Receptor Protein-Tyrosine Kinases
KW - Retrospective Studies
KW - Risk Factors
KW - Signal Transducing
KW - Signal Transduction
KW - Time Factors
KW - Tissue Array Analysis
KW - Transcription Factors
KW - Tumor
UR - https://publicatt.unicatt.it/handle/10807/111904
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85014261275&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85014261275&origin=inward
U2 - 10.1002/jcp.25745
DO - 10.1002/jcp.25745
M3 - Article
SN - 0021-9541
VL - 232
SP - 2246
EP - 2252
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 8
ER -