Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug;194(3):569-575.
doi: 10.1007/s10549-022-06660-x. Epub 2022 Jul 4.

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

Neelima Vidula  1 , Christina Yau #  2 , Hope Rugo #  2
Affiliations

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

Neelima Vidula et al. Breast Cancer Res Treat. 2022 Aug.

Abstract

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.

Keywords: Breast Cancer; TACSTD2 gene expression; TROP2; Triple-negative breast cancer.

PubMed Disclaimer

References

    1. Shvartsur A, Bonavida B (2015) Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer 6(3–4):84–105. https://doi.org/10.18632/genesandcancer.40 - DOI - PubMed - PMC
    1. Zhao W, Kuai X, Zhou X, Jia L, Wang J, Yang X, Tian Z, Wang X, Lv Q, Wang B, Zhao Y, Huang W (2018) Trop2 is a potential biomarker for the promotion of EMT in human breast cancer. Oncol Rep 40(2):759–766. https://doi.org/10.3892/or.2018.6496 - DOI - PubMed
    1. Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM (2015) Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget 6(26):22496–22512. https://doi.org/10.18632/oncotarget.4318 - DOI - PubMed - PMC
    1. Lin H, Zhang H, Wang J, Lu M, Zheng F, Wang C, Tang X, Xu N, Chen R, Zhang D, Zhao P, Zhu J, Mao Y, Feng Z (2014) A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo. Int J Cancer 134(5):1239–1249. https://doi.org/10.1002/ijc.28451 - DOI - PubMed
    1. Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O’Shaughnessy J, Kalinsky K, Guarino M, Abramson V, Juric D, Tolaney SM, Berlin J, Messersmith WA, Ocean AJ, Wegener WA, Maliakal P, Sharkey RM, Govindan SV, Goldenberg DM, Vahdat LT (2017) Efficacy and safety of anti-trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol 35(19):2141–2148. https://doi.org/10.1200/jco.2016.70.8297 - DOI - PubMed - PMC

LinkOut - more resources