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Background <p>TROP2 has recently emerged as a promising therapeutic target, with the antibody‒drug conjugate sacituzumab govitecan. Nevertheless, its biological and clinical relevance in urothelial carcinoma (UC) has not been fully investigated.</p> Methods <p>We evaluated TROP2 protein expression in 114 upper tract UC (UTUC) tissue samples using immunohistochemistry. RNA-seq–based in silico analyses was further performed.</p> Results <p>TROP2 expression was predominantly restricted to tumor tissues and was observed in 72 of 114 cases (63%). TROP2 overexpression was associated with papillary morphology, low tumor grade, early pathological T stage, and favorable clinical outcome. Notably, high TROP2 expression was identified as an independent prognostic factor. Additionally, TROP2 expression showed positive correlations with both UPK3 and Nectin-4 expression. In silico analyses further supported these findings, showing that <i>TACSTD2</i> (the gene encoding TROP2) expression was significantly elevated in tumors of lower stage, low grade, papillary morphology, luminal subtype, and <i>FGFR3</i>-mutated cases, and was correlated with improved prognosis when the Hiroshima cohort–derived cutoff was applied. Furthermore, a significant correlation between <i>TACSTD2</i> and <i>NECTIN4</i> gene expression was observed. Bioinformatics analysis using RNA-Seq datasets revealed that the <i>TACSTD2</i> high group was significantly enriched in gene sets related to tumor metabolic reprogramming, whereas TACSTD2-low tumors showed signatures related to extracellular matrix remodeling and epithelial–mesenchymal transition (EMT).</p> Conclusions <p>Our findings underscore the clinical significance of TROP2 expression in UTUC and suggest that IHC-based evaluation may contribute to prognostic risk stratification.</p>

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TROP2 expression is associated with early stage and favorable prognosis in upper tract urothelial carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月13日

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  • Go Kobayashi,
  • Yohei Sekino,
  • Tetsutaro Hayashi,
  • Hikaru Nakahara,
  • Kohei Kobatake,
  • Hiroyuki Kitano,
  • Keisuke Goto,
  • Hiroaki Niitsu,
  • Takao Hinoi,
  • Kazuhiro Sentani,
  • Nobuyuki Hinata

摘要

Background

TROP2 has recently emerged as a promising therapeutic target, with the antibody‒drug conjugate sacituzumab govitecan. Nevertheless, its biological and clinical relevance in urothelial carcinoma (UC) has not been fully investigated.

Methods

We evaluated TROP2 protein expression in 114 upper tract UC (UTUC) tissue samples using immunohistochemistry. RNA-seq–based in silico analyses was further performed.

Results

TROP2 expression was predominantly restricted to tumor tissues and was observed in 72 of 114 cases (63%). TROP2 overexpression was associated with papillary morphology, low tumor grade, early pathological T stage, and favorable clinical outcome. Notably, high TROP2 expression was identified as an independent prognostic factor. Additionally, TROP2 expression showed positive correlations with both UPK3 and Nectin-4 expression. In silico analyses further supported these findings, showing that TACSTD2 (the gene encoding TROP2) expression was significantly elevated in tumors of lower stage, low grade, papillary morphology, luminal subtype, and FGFR3-mutated cases, and was correlated with improved prognosis when the Hiroshima cohort–derived cutoff was applied. Furthermore, a significant correlation between TACSTD2 and NECTIN4 gene expression was observed. Bioinformatics analysis using RNA-Seq datasets revealed that the TACSTD2 high group was significantly enriched in gene sets related to tumor metabolic reprogramming, whereas TACSTD2-low tumors showed signatures related to extracellular matrix remodeling and epithelial–mesenchymal transition (EMT).

Conclusions

Our findings underscore the clinical significance of TROP2 expression in UTUC and suggest that IHC-based evaluation may contribute to prognostic risk stratification.