High Levels of Nucleolar Spindle-Associated Protein and Reduced Levels of BRCA1 Expression Predict Poor Prognosis in Triple-Negative Breast Cancer.
OBJECTIVE
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.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Li
L
Chen
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Liu
L
Yang
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Feng
F
Qiao
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Xin
X
Hu
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Shan
S
Li
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Ling
L
Yao
Department of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Xue-Li
XL
Yang
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Zhi-Ming
ZM
Shao
D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; D011980:Receptors, Progesterone