Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: a systematic review and meta-analysis

Abstract

Background Nestin 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. Methods A 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. Results A 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). Conclusions This 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.

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

“…As TNBCs do not express the ER, HER-2 and PR genes, they do not respond to available targeted agents and endocrine therapy [3,19], making it challenging to treat this malignancy. TNBC patients show a shorter median time to relapse and death [20].…”

Knockdown of the prognostic cancer stem cell marker Musashi-1 decreases radio-resistance while enhancing apoptosis in hormone receptor-positive breast cancer cells via p21WAF1/CIP1

“…While there was only a positive trend between MSI-1 and Nestin expression in MCF-7 cells, the correlation met levels of significance in the dataset analysis. Nestin is an independent predictor of worse prognosis in breast cancer (Zhang et al 2020).…”

SOX2 Promotes Cell Proliferation and Metastasis in Triple Negative Breast Cancer

“…Triple negative breast cancer is a heterogeneous disease characterized by aberrations at genomic or molecular levels resulting in a great multitude of dysregulated signaling pathways ( Jiang et al, 2014 ; Hon et al, 2016 ). SRY-related HMG box-containing transcription factor-2 (SOX2) is one of these abnormal expressed genes in many cancers including breast cancer ( Zheng et al, 2015 ). SOX2 is a key transcription factor and plays an extremely important role in maintaining pluripotency of stem cells.…”