Tumor-associated calcium signal transducer 2 expression as a promising therapeutic target in esophageal squamous cell carcinoma: a combined the Cancer Genome Atlas and an institutional cohort

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, and new therapeutic targets are required. Antibody–drug conjugates (ADCs) are a promising therapeutic modality that selectively delivers cytotoxic payloads to tumors via cell-surface antigens. Tumor-associated calcium signal transducer 2 (TROP2, TACSTD2 ) has shown therapeutic potential as an ADC target in several malignancies; however, its clinical significance in ESCC remains unclear. Methods An institutional cohort of ESCC patients treated at Kindai University was retrospectively evaluated by immunohistochemistry (n=70) and RNA sequencing (n=27). TACSTD2 copy number alterations, RNA expression, and survival were analyzed using the Cancer Genome Atlas (TCGA) ESCC dataset. IHC was assessed in both resected and biopsy specimens, including metastatic lesions. Survival analyses were performed, stratifying patients by cohort-specific median TACSTD2 expression levels. Results Immunohistochemistry analysis demonstrated uniformly strong TROP2 expression in all evaluable primary and metastatic lesions. In the TCGA dataset, TACSTD2 mRNA expression was consistently high, irrespective of copy-number status, and was comparable to or higher than that observed in non-small cell lung cancer and breast cancer, tumor types in which TROP2-targeted ADCs are clinically active. The TACSTD2 high-expression group showed a trend toward worse overall survival in both the institutional and the TCGA cohort, whereas disease-free survival was similar. Conclusions TROP2/ TACSTD2 is strongly and consistently expressed in ESCC at the protein and RNA levels, despite infrequent gene amplification, supporting its feasibility as a therapeutic target. High expression shows a trend toward poorer overall survival, warranting validation in larger cohorts.