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.
Highlights
Breast cancer, which adversely affects women’s physical and psychological health, has the highest incidence of female malignant tumors
It is normally primarily found in the cytoplasm, and during the apoptotic process, it is transported into the nucleus to interact with its nuclear substrates [41]
Because of the role of caspase-3 in apoptosis, some researchers suggest that its reduced expression might result in tumor cells escaping from apoptosis and lead to tumorigenesis and deterioration [36, 42]
Summary
Breast cancer, which adversely affects women’s physical and psychological health, has the highest incidence of female malignant tumors. It is necessary to identify a more valuable and convenient biomarker that can be tested in early breast cancer, used to reduce the disease mortality. Several studies have reported that breast cancers with a high apoptosis index have a better prognosis than those with lower or absent levels of apoptosis [2,3,4,5]. (ADP-ribose) polymerase 1 (PARP-1) is responsible for DNA repair and programmed cell death and is the most important substrate of caspase-3. During the early stages of apoptosis, caspase-3 is cleaved into 29- and 85-kDa fragments [8] by PARP-1. Cleavage of caspase-3 was shown to mediate tumor repopulation in apoptotic tumor cells [9]. The change of caspase-3 expression is related to the carcinogenesis and progression of many tumors, such as colon cancer [10], cervical adenocarcinoma [11], and glioma [12], indicating that caspase-3 level may be a useful biomarker for these tumors
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