Caspase-3 over-expression is associated with poor overall survival and clinicopathological parameters in breast cancer: a meta-analysis of 3091 cases

Abstract

Caspase-3 is a vital executioner molecule during the apoptotic process. Numerous studies have revealed the close association of caspase-3 expression and breast cancer. Nevertheless, the prognostic value of caspase-3 expression for patients with breast cancer remains uncertain. To thoroughly analyze the prognostic effect of caspase-3 expression on the clinicopathological features and survival of breast cancer, we conducted this meta-analysis. With various search strategies, electronic databases were comprehensively searched. A total of 3091 patients from 21 studies were ultimately obtained. The analysis results indicated that increased expression of caspase-3 had a negative influence on the overall survival (OS) of breast cancer (HR = 1.73, 95%CI 1.12–2.67, P = 0.014). Subgroup analyses based on race revealed that the value of caspase-3 for evaluating patients’ OS was more useful in Asian patients (HR = 3.16, 95%CI 1.20–8.15, P = 0.020), and subgroup analyses based on study analytical methods revealed that caspase-3 was a risk factor for breast cancer patients in multivariate overall survival analyses (HR = 1.67, 95%CI 1.02–2.75, P = 0.044). As for the relationship between caspase-3 expression and breast cancer subtype as well as progression, caspase-3 might serve as a risk factor for the progestogen receptor (PR) and human epidermal growth factor receptor-2 (HER-2) subtypes (OR = 1.44, 95%CI 1.09–1.89, P = 0.010; OR = 1.76, 95%CI 1.18–2.62, P = 0.050, respectively) of breast cancer. However, no evidence showed that increased expression of caspase-3 was statistically correlated with tumor differentiation state (low/moderate or high), tumor TNM stage (I-II/III-IV) or lymph node metastasis (–/+). In conclusion, this meta-analysis revealed that increased caspase-3 expression was significantly associated with worse prognosis and two subtypes of breast cancer. More prospective studies are urgently needed to define the prognostic value of caspase-3 expression in patients with breast cancer.