Abstract
BackgroundNestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Therefore, we performed this meta-analysis to elucidate the prognostic and clinicopathological association of nestin expression with breast cancer.MethodsA comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.ResultsA total of 15 studies with 6066 breast cancer patients were included in this meta-analysis. Pooled results indicated that positive expression of nestin was significantly associated with reduced breast cancer-specific survival (BCSS, univariate analysis, HR = 2.11, 95% CI [1.79, 2.49], P < 0.00001; multivariate analysis, HR = 1.30, 95% CI [1.06, 1.60], P = 0.01), worse overall survival (OS, univariate analysis, HR = 1.88, 95% CI [1.31, 2.71], P = 0.0007; multivariate analysis, HR = 1.89, 95% CI [1.34, 2.67], P = 0.0003) and poorer recurrence-free survival (univariate analysis, HR = 2.60, 95% CI [1.52, 4.46], P = 0.0005), but not with distant metastasis-free survival in univariate analysis (P > 0.05). In addition, increased nestin expression was correlated with younger age, higher tumor grade, larger tumor size, positive blood vessel invasion and high vascular proliferation index, but not with lymph node metastasis or lymph vessel invasion. Nestin was preferentially expressed in invasive ductal carcinoma, triple-negative breast cancer and basal-like subtypes. Nestin expression was inversely associated with the expression of ER and PR, but not with HER-2. Conversely, nestin expression was positively correlated with the expression of basal-like markers CK5, P-cadherin and EGFR. Moreover, nestin expression was strongly associated with the presence of five basal-like profiles (BLP1-5).ConclusionsThis meta-analysis revealed the prognostic value and clinicopathological significance of nestin expression in breast cancer. Nestin is an independent prognostic factor for worse BCSS and OS of breast cancer patients. Nestin is also a valuable biomarker for unfavorable clinicopathological features and tumor angiogenesis of breast cancer. Therefore, nestin is a promising therapeutic target for malignant breast cancer, especially for TNBC and basal-like phenotype.
Highlights
Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer
Histopathological classification of Breast cancer (BC) was primarily based on immunohistochemical (IHC) detection of four molecular markers implicated in growth signaling pathways: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki-67 [4, 5]
Studies were eligible if they met the following criteria: (a) studies were published as original articles with full text available; (b) definitive diagnosis of breast cancer was confirmed by histopathological examination; (c) nestin expression was detected by an immunohistochemistry (IHC) method or quantitative real-time polymerase chain reaction method based on breast cancer tissues, and (d) the correlation of nestin expression with clinicopathological features or prognostic outcomes was analyzed
Summary
Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. The prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Gene expression profiling can more precisely and systematically sort BC into five intrinsic molecular subtypes: luminal A, luminal B, HER2-enriched, basallike and normal-like BC [7, 8]. Among these subtypes, basal-like subtype accounts for 15% of all invasive breast cancer and is characterized by highly aggressive behaviors, poor differentiation and lack of molecular targets for endocrine and anti-HER2 therapies [7,8,9,10]. It is imperative to uncover the molecular mechanisms underlying the relapse and metastasis of malignant breast cancer and explore novel therapeutic targets to improve the management of breast cancer patients [20]
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