Abstract 434: Circulating visfatin promotes malignant cancer behavior through activation of STAT3 signaling in breast cancer
Authors: Shyng-Shiou F. Yuan, Amos C. Hung, Ming-Feng Hou
Journal: Cancer Research (2014)

Abstract Adipocytokines are adipocyte-derived hormones which have been shown potentially associated with carcinogenesis. In this study, the role of circulating visfatin, a recently discovered adipocytokine involving in breast cancer progression, was investigated. Our data showed that the levels of serum visfatin in breast cancer patients were closely correlated with several clinicopathological characteristics including tumor stages, tumor size, and lymph node (LN) metastasis. In addition, differential association of disease recurrence and patients survival with hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (Her2/Neu) were observed. Patients with high serum visfatin, especially in combination with ER- status, showed the lowest survival rate. Furthermore, high serum visfatin patients had a lower recurrence risk and better patient survival after adjuvant hormone therapy. Notably, serum visfatin was positively associated with STAT3 activation through tyrosine phosphorylation in breast cancer tissues. In agreement with the clinical observation, our in vitro data revealed that breast cancer cells treated with visfatin not only enhanced cell proliferation but also activated STAT3 and its upstream regulator, JAK1. Moreover, inhibition of STAT3 resulted in the reduced cell proliferation and invasive ability of breast cancer cells. In conclusion, we propose that high levels of circulating visfatin, probably via activation of STAT3 signaling pathway, lead to a malignant cancer progression and poor survival of breast cancer patients. Therefore, the visfatin/STAT3 pathway may constitute a valuable prognostic system for breast cancer patients. In addition, interference of the visfatin/STAT3 signaling may represent a novel therapeutic potential in the treatment of breast cancer. Table 1. Univariate and multivariable analysis of overall survival for breast cancerVariablesItemUnivariateMultivariable†Hazard Rate Ratio95% Confidence intervalP valueHazard Rate Ratio95% Confidence intervalP valueTumor size (cm)&amp;gt;54.36(1.69,11.27)0.0022.13(0.79,5.74)0.1362-52.47(1.05,5.81)0.0391.68(0.70,4.05)0.245&amp;lt;21.001.00LN Metastasis≥23.34(1.75,6.37)&amp;lt;0.0012.43(1.25,4.72)0.0090-11.001.00GradeIII2.47(0.81,7.53)0.112---II1.56(0.53,4.55)0.419--I1.00-Age(y)&amp;gt;501.49(0.81,2.73)0.197---≤501.00-BMI(kg/m2)&amp;lt;241.14(0.60,2.14)0.690---≥241.00-Her2/NeuPositive1.14(0.60,2.17)0.699---Negative1.00-RadiotherapyYes1.11(0.60,2.03)0.744---No1.00-ChemotherapyYes0.89(0.41,1.93)0.774---No1.00-HormoneTherapyYes0.36(0.20,0.66)0.0010.46(0.24,0.87)0.017No1.001.00VisfatinHigh5.67(2.01,15.98)0.0013.55(1.22,10.36)0.020Low1.001.00† Variables with P values greater than 0.10 in the univariate analysis were excluded from multivariable analysis. Citation Format: Shyng-Shiou F. Yuan, Amos C. Hung, Ming-Feng Hou. Circulating visfatin promotes malignant cancer behavior through activation of STAT3 signaling in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 434. doi:10.1158/1538-7445.AM2014-434