J Breast Cancer.  2019 Jun;22(2):248-259. 10.4048/jbc.2019.22.e20.

High Survivin and Low Zinc Finger of the Cerebellum 1 Expression Indicates Poor Prognosis in Triple-negative Breast Carcinoma

• Shi CT
• Ma J
• Shi QF
• Zhang Y
• Wang HN

• KMID: 2450119
• DOI: http://doi.org/10.4048/jbc.2019.22.e20

Abstract

PURPOSE
Triple-negative breast carcinoma (TNBC) is accompanied with high risk of metastasis and recurrence. The present study aimed to explore the clinicopathological and prognostic roles of putative tumor-related genes in patients with TNBC.
METHODS
Thirty pairs of frozen-thawed tumors were used to select reliable indicators via real-time quantitative polymerase chain reaction (RT-qPCR). Then, 150 pathology specimens were used to evaluate the expression of proteins in TNBC through immunohistochemistry. In addition, Kaplan-Meier curves and Cox regression analysis were also performed to analyze the overall survival and disease-free survival.
RESULTS
RT-qPCR results indicated that among all the proteins analyzed using fresh-frozen TNBC samples, the expression levels of only Survivin and zinc finger of the cerebellum 1 (ZIC1) were obviously different from those in the corresponding normal tissues. Survivin and ZIC1 expression had opposite effects on the clinicopathological diagnosis and prognostic assessment in TNBC patients. Further, there was a negative correlation between Survivin and ZIC1 expression. In addition, the "Survivin-positive ZIC1-negative group" was associated with histologic grade, lymph node metastasis, and TNM staging (p < 0.001) and this was also an independent factor for evaluating the prognosis of TNBC in patients.
CONCLUSION
In summary, the expression levels of Survivin and ZIC1 in TNBC are different from those in normal tissues and are negatively correlated mutually. The combined detection of Survivin and ZIC1 expression levels could allow better comprehensive diagnosis and prognostic evaluation for TNBC patients.

Keyword

Prognosis; Survivin; Triple negative breast neoplasms; ZIC1 protein, human

MeSH Terms

Breast Neoplasms*
Breast*
Cerebellum*
Diagnosis
Disease-Free Survival
Humans
Immunohistochemistry
Lymph Nodes
Neoplasm Metastasis
Neoplasm Staging
Pathology
Polymerase Chain Reaction
Prognosis*
Recurrence
Triple Negative Breast Neoplasms
Zinc Fingers*
Zinc*
Zinc

Figure

• 

  Figure 1 The result of RT-qPCR of IAPs (Survivin and livin), eIF3 subunits, NM23 genes and ZIC family genes. RT-qPCR = real-time quantitative polymerase chain reaction; IAP = inhibitors of apoptosis; eIF3 = eukaryotic initiation factor 3; NM23 = non-metastatic 23; ZIC = zinc finger of the cerebellum. *p<0.001.

• 

  Figure 2 The expression of Survivin and ZIC1 in TNBC patients. (A) Survivin protein was observed in the nucleus and cytoplasm of TNBC (IHC for Survivin, ×400); (B) Survivin protein was observed in the nucleus and cytoplasm of normal tissues (IHC for Survivin, ×400); (C) ZIC1 protein was observed in the cytoplasm of TNBC (IHC for ZIC1, ×400); (D) ZIC1 protein was observed in the cytoplasm of normal tissues (IHC for ZIC1, ×400); (E) Comparison of Survivin IRS and ZIC1 IRS in TNBC with normal tissues; (F) a negative correlation between Survivin and ZIC1 expression, r = −0.3768, p < 0.001. IRS = immunoreactivity score; ZIC = zinc finger of the cerebellum; TNBC = triple-negative breast carcinoma; IHC = immunohistochemistry. *p < 0.01.

• 

  Figure 3 Kaplan-Meier survival curves of TNBC patients divided by Survivin or ZIC1 expression. (A) overall survival divided by Survivin expression; (B) overall survival divided by ZIC1 expression; (C) disease-free survival divided by Survivin expression; (D) disease-free survival divided by ZIC1 expression. ZIC = zinc finger of the cerebellum; TNBC = triple-negative breast carcinoma.

• 

  Figure 4 Kaplan-Meier survival curves of TNBC patients (“Survivin positive and ZIC1 negative expression” vs others). (A) overall survival; (B) disease-free survival. ZIC = zinc finger of the cerebellum; TNBC = triple-negative breast carcinoma.

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