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Peer-reviewedCC BY 4.0Esophagus

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

  • Chiaki Inagaki1,2
  • Hisato Kawakami1,3
  • Seiichiro Mitani1
  • Hiroshi Iijima4
  • Ryo Matoba4
  • Akihiko Ito5
  • Osamu Shiraisi6
  • Takushi Yasuda6
  • Hidetoshi Hayashi1
6 affiliations
  1. 1Department of Medical Oncology, Faculty of Medicine, Kindai University, 1-14-1 Miharadai, Minami-Ku, Sakai-Shi, Osaka, Japan
  2. 2Genome Medical Center, Kindai University Hospital, 1-14-1 Miharadai, Minami-Ku, Sakai-Shi, Osaka, Japan
  3. 3Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
  4. 4DNA Chip Research Inc., 3-1200, Shinmaruko-Higashi, KDX Musashikosugi Blgd. 9 F, Nakahara-Ku, Kawasaki-Shi, Kanagaaw, 211-0004 Japan
  5. 5Department of Medicine/Graduate School of Medical Sciences, Faculty of Medicine, Kindai University, 1-14-1 Miharadai, Minami-Ku, Sakai-Shi, Osaka, Japan
  6. 6Department of Surgery, Faculty of Medicine, Kindai University, 1-14-1 Miharadai, Minami-Ku, Sakai-Shi, Osaka, Japan
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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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10388-026-01257-5.

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Cite

BibTeXRIS
BibTeX
@article{inagaki2026tumorassociated,
  title = {{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}},
  author = {Chiaki Inagaki and Hisato Kawakami and Seiichiro Mitani and Hiroshi Iijima and Ryo Matoba and Akihiko Ito and Osamu Shiraisi and Takushi Yasuda and Hidetoshi Hayashi},
  journal = {Esophagus},
  year = {2026},
  month = sep,
  doi = {10.1007/s10388-026-01257-5},
  url = {https://doi.org/10.1007/s10388-026-01257-5},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - 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
AU  - Chiaki Inagaki
AU  - Hisato Kawakami
AU  - Seiichiro Mitani
AU  - Hiroshi Iijima
AU  - Ryo Matoba
AU  - Akihiko Ito
AU  - Osamu Shiraisi
AU  - Takushi Yasuda
AU  - Hidetoshi Hayashi
PY  - 2026
DA  - 2026/09/20
JO  - Esophagus
DO  - 10.1007/s10388-026-01257-5
UR  - https://doi.org/10.1007/s10388-026-01257-5
AB  - 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10388-026-01257-5.
SN  - 1612-9059
SN  - 1612-9067
ER  -