High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer

Li Chen; Liu Yang; Feng Qiao; Xin Hu; Shan Li; Ling Yao; Xue-Li Yang; Zhi-Ming Shao

doi:10.1371/journal.pone.0140572

High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer

PLoS One. 2015 Oct 20;10(10):e0140572. doi: 10.1371/journal.pone.0140572. eCollection 2015.

Authors

Li Chen¹, Liu Yang¹, Feng Qiao², Xin Hu², Shan Li², Ling Yao², Xue-Li Yang³, Zhi-Ming Shao¹

Affiliations

¹ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
³ Department of Cancer Stem Cell, Dalian Medical University, Dalian, China.

Abstract

Purpose: Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.

Methods: Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.

Results: There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956-8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160-0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).

Conclusions: Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
BRCA1 Protein / genetics
BRCA1 Protein / metabolism*
Biomarkers, Tumor / metabolism
Disease-Free Survival
Female
Humans
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Middle Aged
Prognosis
Receptors, Progesterone / metabolism
Triple Negative Breast Neoplasms / genetics
Triple Negative Breast Neoplasms / metabolism*
Triple Negative Breast Neoplasms / mortality
Triple Negative Breast Neoplasms / pathology

Substances

BRCA1 Protein
BRCA1 protein, human
Biomarkers, Tumor
Microtubule-Associated Proteins
NUSAP1 protein, human
Receptors, Progesterone

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81201531), the 2012 Shanghai Committee of Science and Technology Funds (12ZR1406200, 12DZ2260100 and 12140901502) and the Shanghai Committee of Science and Technology Fund for the 2013 Qimingxing Project (13QA1400900 to X. Hu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.