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

Xinyi Zhang; Changsheng Xing; Wenting Guan; Lang Chen; Kai Guo; Anze Yu; Kai Xie

doi:10.1186/s12935-020-01252-5

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

Cancer Cell Int. 2020 May 14:20:169. doi: 10.1186/s12935-020-01252-5. eCollection 2020.

Authors

Xinyi Zhang^{1

2

3}, Changsheng Xing⁴, Wenting Guan^{5

6}, Lang Chen^{4

7}, Kai Guo⁸, Anze Yu^{4

9}, Kai Xie^{4

10

11}

Affiliations

¹ 1Department of Cardiovascular Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 China.
² 2Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, 410008 China.
³ 3The Third Xiangya Hospital, Central South University, Changsha, 410013 China.
⁴ 4Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030 USA.
⁵ 5Department of Radiology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300 China.
⁶ 6Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009 China.
⁷ 7Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, 410013 China.
⁸ 8Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008 China.
⁹ 9Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008 China.
¹⁰ 10Department of General Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 China.
¹¹ 11Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008 China.

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.

Keywords: Breast cancer; Clinicopathological characteristics; Meta-analysis; Nestin; Prognosis.