GATA3 and TRPS1 are distinct biomarkers and prognostic factors in breast cancer: database mining for GATA family members in malignancies

Abstract

GATA transcription factors are zinc finger DNA binding proteins that activate transcription during development and cell differentiation. To date, 7 members of GATA family have been reported. However, the expression patterns and the exact roles of distinct GATA family members contributing to tumorigenesis and progression of breast cancer (BC) remain to be elucidated. Here, we studied the expression of GATA transcripts in a variety of tumor types compared with the normal controls using the ONCOMINE and GOBO databases, along with their corresponding expression profiles in an array of cancer cell lines through CCLE analysis. Based on Kaplan-Meier plotter, we further investigated the prognostic values of GATA members specifically high expressed in BC patients. It was found that, when compared with normal tissues, GATA3 and TRPS1 were distinctly high expressed in BC patients among all GATA members. GATA3 expression was significantly associated with ESR1, while TRPS1 was correlated with ERBB2. In survival analysis, GATA3 and TRPS1 mRNA high expressions were correlated to better survival in BC patients, and TRPS1 high expression was significantly associated with longer RFS in patients who have received chemotherapy. These results suggest that GATA3 and TRPS1 are distinct biomarkers and essential prognostic factors for breast cancer.

Keywords: GATA; breast cancer; chemosensitivity; database mining; prognostic values.

Figure 1. The mRNA expression pattern of GATA family members in different tumor types

This graphic showed the numbers of datasets with statistically significant mRNA over-expression (red) or down-expression (blue) of the target gene (cancer vs. normal tissue). The p value threshold is 0.01. The number in each cell represents the number of analyses that meet the threshold within those analysis and cancer types. The gene rank was analyzed by percentile of target gene in the top of all genes measured in each research. Cell color is determined by the best gene rank percentile for the analyses within the cell.

Figure 2. GATA family analysis in Breast cancer (ONCOMINE database)

Box plots derived from gene expression data in ONCOMINE comparing expression of a specific GATA family member in normal and BC tissue. The p value was set up at 0.01 and fold change was defined as 2. (A) Comparison of GATA1 mRNA expression. (B) Comparison of GATA2 mRNA expression. (C-D) Comparison of GATA3 mRNA expression. (E) Comparison of GATA4 mRNA expression. (F) Comparison of GATA5 mRNA expression. (G) Comparison of GATA6 mRNA expression. (H) Comparison of TRPS1 mRNA expression.

Figure 3. GATA3 and TRPS1 were distinctively high expressed in breast cancer cell lines from CCLE analysis

(A) The mRNA expression level of GATA3 ranked the third highest in a variety of cancer cell line, behind that of retinoblastoma and T-cell-ALL, (shown in red frame). (B) The mRNA expression level of TRPS1 ranked the highest in breast cancer among different cancer cell types, (shown in red frame).

Figure 4. The correlation analysis of GATA3 in different molecular subtypes of breast cancer

(A) In ONCOMINE analysis, the expression of GATA3 was significantly associated with ESR1 expression. (shown in red frame) (B) The expression of GATA3 in luminal-like was significantly higher than in basal-like subtypes of breast cancer. (C) In CCLE analysis, GATA3 over-expressed in the breast cancer cell lines with high level of ER expression, while under-expressed in those with low level or negative ER expression. (D) In GOBO analysis, the expression of GATA3 in luminal-like was significantly higher than in basal A or Basal B subtypes of breast cancer, and the Hormone Receptor (HR) subtype also express higher GATA3 than TN(Triple Negative) and HER2 clinical subtypes. (E) the expression of GATA3 in each cell lines.

Figure 5. The correlation analysis of GATA3 in different molecular subtypes of breast cancer

(A) In ONCOMINE analysis, TRPS1 expression was significantly correlated with ERBB2 expression. (shown in red frame) (B) In CCLE analysis, TRPS1 over-expressed in the breast cancer cell lines with high level of ERBB2 expression, while under-expressed in those with low level or negative ERBB2 expression. (C) In GOBO analysis, the expression of TRPS1 in different subtypes of breast cancer (E) the expression of TRPS1 in each cell lines.

Figure 6. The prognostic values of GATA3 in breast cancer

(A) High mRNA level of GATA3 was associated with longer RFS in all BC patients. (B) High mRNA level of GATA3 was associated with longer RFS both in ER+, but not ER- BC patients. (C) High mRNA level of GATA3 was associated with longer RFS in luminal A subtype BC patients, but not in luminal B subtype BC patients. (D) High mRNA level of GATA3 was not associated with RFS in either HER-2 positive or basal-like subtype BC patients.

Figure 7. The prognostic values of mRNA level of TRPS1 in breast cancer patients

(A) High mRNA level of TRPS1 was associated with longer RFS in all BC patients. (B) High mRNA level of TRPS1 was associated with longer RFS both in ER positive, but not in ER negative BC patients. (C) High mRNA level of TRPS1 was associated with longer RFS in luminal subtypes BC patients. (D) High mRNA level of TRPS1 is not associated with longer RFS in either luminal B or basal-like subtype BC patients. (E) High mRNA level of TRPS1 is associated with longer RFS in BC patients, who have received chemotherapy, while not associated with RFS in those haven't received chemotherapy.