Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer.

Abstract

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. 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. 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. 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.