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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer
Neelima Vidula1, Christina Yau2, Hope Rugo2
1Massachusetts General Hospital Cancer Center, 55 Fruit Street, Bartlett Hall Extension 1-213, Boston, MA, USA. nvidula@mgh.harvard.edu.
Purpose:
Trophoblast Cell Surface Antigen 2 (TROP2) is a glycoprotein expressed in many cancers. A TROP2 antibody-drug conjugate (ADC) was effective in metastatic triple-negative breast cancer (TNBC). We studied TROP2 gene (TACSTD2) expression and associations with tumor and clinical characteristics, as well as selected external genes in primary breast cancer.
Methods:
TACSTD2 gene expression was evaluated using microarray data from I-SPY 1 (n = 149), METABRIC (n = 1992), and TCGA (n = 817). Associations with clinical features (Kruskal-Wallis test, all datasets), chemotherapy response (Wilcoxon rank sum test, I-SPY 1), recurrence free survival (Cox proportional hazard model, I-SPY 1 and METABRIC), and selected genes (Pearson correlations, all datasets) were determined.
Results:
TACSTD2 gene expression was detectable in all breast cancer subtypes, with a wide range of expression (all datasets). TACSTD2 gene expression was lower in HER2 + than HR + /HER2- and TNBC (METABRIC: p = 0.03, TCGA p = 0.007), and in HER2 + enriched and luminal B breast cancer (METABRIC: p < 0.001, TCGA: p < 0.001). TACSTD2 expression was higher in grade I vs. II/III tumors (METABRIC: p < 0.001). No association with chemotherapy response (I-SPY 1) or recurrence free survival (I-SPY 1 and METABRIC) was seen. TACSTD2 has significant positive correlations with the expression of epithelial/adhesion genes and proliferative genes, but was inversely correlated with immune genes.
Conclusion:
TACSTD2 gene expression was seen in all breast cancer subtypes particularly luminal A and TNBC, and correlated with the expression of genes involved in cell epithelial transformation, adhesion, and proliferation, which contribute to tumor growth. These results support the investigation of TROP2 ADC in all subtypes of breast cancer.
Insights
Trophoblast cell surface antigen 2 (TROP2) gene expression occurs across all breast cancer subtypes. TACSTD2 expression correlates with genes promoting tumor growth, supporting TROP2 antibody-drug conjugate investigation in all breast cancer types.
Area of Science:
- Oncology
- Genomics
- Biomarker Research
Background:
- Trophoblast cell surface antigen 2 (TROP2) is a cell surface glycoprotein implicated in various cancers.
- A TROP2 antibody-drug conjugate (ADC) has demonstrated efficacy in metastatic triple-negative breast cancer (TNBC).
- Understanding TACSTD2 gene expression is crucial for evaluating TROP2-targeted therapies in breast cancer.
Purpose of the Study:
- To investigate Trophoblast cell surface antigen 2 (TROP2) gene (TACSTD2) expression in primary breast cancer.
- To analyze associations between TACSTD2 expression and tumor characteristics, clinical features, and other gene expressions.
- To assess the potential of TROP2-targeted therapies across diverse breast cancer subtypes.
Main Methods:
- TACSTD2 gene expression was analyzed using microarray data from three independent cohorts: I-SPY 1 (n=149), METABRIC (n=1992), and TCGA (n=817).
- Statistical analyses included Kruskal-Wallis tests for clinical features, Wilcoxon rank sum test for chemotherapy response, Cox proportional hazard models for survival, and Pearson correlations for gene associations.
- Expression levels were compared across breast cancer subtypes, grades, and correlated with clinical and molecular features.
Main Results:
- TACSTD2 gene expression was detected in all breast cancer subtypes, exhibiting a broad range.
- Lower TACSTD2 expression was observed in HER2-positive breast cancer compared to HR+/HER2- and TNBC subtypes.
- TACSTD2 expression positively correlated with epithelial/adhesion and proliferative genes, but inversely with immune genes, and showed no significant association with chemotherapy response or recurrence-free survival.
Conclusions:
- TACSTD2 gene is expressed across all breast cancer subtypes, notably in luminal A and TNBC.
- TACSTD2 expression correlates with genes involved in epithelial transformation, adhesion, and proliferation, suggesting a role in tumor growth.
- These findings support the exploration of TROP2 antibody-drug conjugates (ADCs) for treating all breast cancer subtypes.
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