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Background <p>The aim of this study is to better characterize the expression profiles of well-established tumor-associated antigen (TAA) for antibody-drug conjugates (ADC) in primary lesion (PL) and bone metastatic lesion(BML) of prostate cancer (PCa).</p> Methods <p>Mass spectrometry (MS) and immunohistochemistry (IHC) were used to comprehensively compare the expression of HER2, NECTIN4, TROP2, PSMA, TF, STEAP1 and B7H3 in the matched cohort (<i>n</i> = 27 pairs), which included matched PL and BML samples from the same patients. IHC was then used to validate the expression of these TAAs in another independent unmatched cohort, including PL (<i>n</i> = 100) and BML (<i>n</i> = 49). IHC assessment included traditional semi-quantitative evaluation, computer-assisted H-score assessment and normalized membrane ratio (NMR) analysis.</p> Results <p>B7H3, STEAP1 and PSMA consistently exhibited high and stable expression rate in matched PL and BML, whereas the expression levels of the other TAAs may fluctuate between the two status. In the unmatched cohort, the expression levels of TROP2, TF, PSMA, and B7H3 were significantly lower, while the expression levels of HER2 and STEAP1 were significantly higher in BML than in PL (all <i>p</i> &lt; 0.05). Overall, STEAP1, B7H3 and PSMA exhibited high expression rates in BML, with STEAP1 and B7H3 depicting relatively homogeneous high membranous expression patterns. The co-expression of these TAAs was frequently observed. In the dual-TAA combination analysis, any pairwise combination among B7H3, STEAP1, and PSMA exhibited relatively high expression coverage(å 85%) for BML.</p> Conclusions <p>B7H3, STEAP1, and PSMA might be the predominant targets in both PL and BML. Our findings reveal the dynamic and heterogeneous nature of TAA expression in PCa and may provide insights for integrating ADC-based targeted therapies into the existing treatment landscape for PCa.</p>

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Systematic profiling of tumor-associated antigen expression for antibody-drug conjugate in prostate cancer

  • 期刊论文

  • 发表日期：

    2025年12月24日

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  • Yelin Mulati,
  • Qi Shen,
  • Yuke Chen,
  • Yuxuan Tian,
  • Kaifeng Yao,
  • Wei Yu,
  • Yunpeng Cui,
  • Xuedong Shi,
  • Xiaocong Pang,
  • Dongyuan Chang,
  • Zhisong He,
  • Xinan Sheng,
  • Qian Zhang,
  • Yu Fan

摘要

Background

The aim of this study is to better characterize the expression profiles of well-established tumor-associated antigen (TAA) for antibody-drug conjugates (ADC) in primary lesion (PL) and bone metastatic lesion(BML) of prostate cancer (PCa).

Methods

Mass spectrometry (MS) and immunohistochemistry (IHC) were used to comprehensively compare the expression of HER2, NECTIN4, TROP2, PSMA, TF, STEAP1 and B7H3 in the matched cohort (n = 27 pairs), which included matched PL and BML samples from the same patients. IHC was then used to validate the expression of these TAAs in another independent unmatched cohort, including PL (n = 100) and BML (n = 49). IHC assessment included traditional semi-quantitative evaluation, computer-assisted H-score assessment and normalized membrane ratio (NMR) analysis.

Results

B7H3, STEAP1 and PSMA consistently exhibited high and stable expression rate in matched PL and BML, whereas the expression levels of the other TAAs may fluctuate between the two status. In the unmatched cohort, the expression levels of TROP2, TF, PSMA, and B7H3 were significantly lower, while the expression levels of HER2 and STEAP1 were significantly higher in BML than in PL (all p < 0.05). Overall, STEAP1, B7H3 and PSMA exhibited high expression rates in BML, with STEAP1 and B7H3 depicting relatively homogeneous high membranous expression patterns. The co-expression of these TAAs was frequently observed. In the dual-TAA combination analysis, any pairwise combination among B7H3, STEAP1, and PSMA exhibited relatively high expression coverage(å 85%) for BML.

Conclusions

B7H3, STEAP1, and PSMA might be the predominant targets in both PL and BML. Our findings reveal the dynamic and heterogeneous nature of TAA expression in PCa and may provide insights for integrating ADC-based targeted therapies into the existing treatment landscape for PCa.