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.

Abstract

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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