The Prognosis of Signal Transducer and Activator of Transcription 3 Expression On Breast Cancer Survival: a Meta-Analysis and Retrospective Study

Abstract

Background: Signal transducer and activator of transcription 3(STAT3) has been found related to drug resistance and lymph node metastasis in breast cancer. However, it has been found associated with better prognosis in lymph node positive patients. Controversies exist about the prognostic and predictive value of STAT3, as well as its phosphorylated status (p-STAT3) in breast cancer patients. Methods:We performed a meta-analysis including 7 studies retrieved from PubMed database,Web of Science which published up to September 2013. Hazard ratios (HRs) of overall survival (OS) in breast cancer with high STAT3 or p-STAT3 expression versus low expression were collected as original data. HRs with 95% confidence intervals (CIs) were pooled to estimate the overall hazard. Moreover, considering most studies only focus on the expression of STAT3 and p-STAT3 by IHC, we also performed a retrospective study about the relationship between STAT3 gene expression and survival in breast cancer patients using an online web database. Results: A total of 7 published studies (including 2057 patients) were eligible. The results showed that combined STAT3 and p-STAT3 expression have tendency to relate to better OS (HR = 0.71, 95%CI, 0.47, 1.08). Interestingly, p-STAT3 expression was related to better OS (HR = 0.55, 95%CI, 0.35, 0.87), especially in lymph node positive patients .We also found that no matter STAT3 or p-STAT3, only when detected in nucleus, they would predict good survival (HR = 0.52, 95%CI, 0.33, 0.82). Our original study showed that STAT3 gene over-expressed breast cancer patients also had better prognosis compared with STAT3 gene low-expressed patients. Conclusions: p-STAT3 protein over-expression detected by IHC and STAT3 gene over-expression detected by microarray in breast cancer patients appear to have better overall survival. However, these results still need further prospective clinical trials to be clarified.