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

Prostate Cancer and Prostatic Diseases (2025)Cite this article

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Abstract

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.

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Fig. 1: Study workflow of methodology and cohort formation.
Fig. 2: Expression profiles of the well established cell surface TAAs in matched PL and BML.
Fig. 3: Expression profiles of the well established cell surface TAAs in unmatched cohort.
Fig. 4: Head-to-head comparison of TAA membranous H-score in the unmatched cohort.

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Data availability

All data generated or analyzed during this study are included in this article and its supplementary information files. No custom code was developed.

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Acknowledgements

This study was supported by: 1. National Natural Science Foundation of China, General Program, Beijing, China (Grant No. 82370773). 2. National High Level Hospital Clinical Research Funding (Interdepartmental Clinical Research Project of Peking University First Hospital), Beijing, China (2023IR33). 3. National High Level Hospital Clinical Research Funding (Interdepartmental Clinical Research Project of Peking University First Hospital), Beijing, China (2024IR02). 4. Beijing Physician Scientist Training Project, Beijing, China (BJPSTP-2024-20). We would like to thank the Department of Orthopedics and Pathology at Peking University First Hospital for their support and assistance.

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Author notes

  1. These authors contributed equally: Yelin Mulati, Qi Shen.

Authors and Affiliations

  1. Department of urology, Peking University First Hospital, Beijing, China

    Yelin Mulati, Qi Shen, Yuke Chen, Yuxuan Tian, Kaifeng Yao, Wei Yu, Zhisong He, Qian Zhang & Yu Fan

  2. Institute of Urology, Peking University, Beijing, China

    Yelin Mulati, Qi Shen, Yuke Chen, Yuxuan Tian, Kaifeng Yao, Wei Yu, Zhisong He, Qian Zhang & Yu Fan

  3. Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing, China

    Yelin Mulati, Qi Shen, Yuke Chen, Yuxuan Tian, Kaifeng Yao, Wei Yu, Zhisong He, Qian Zhang & Yu Fan

  4. National Urological Cancer Center, Beijing, China

    Yelin Mulati, Qi Shen, Yuke Chen, Yuxuan Tian, Kaifeng Yao, Wei Yu, Zhisong He, Qian Zhang & Yu Fan

  5. Department of Orthopedics, Peking University First Hospital, Beijing, China

    Yunpeng Cui & Xuedong Shi

  6. Department of Pharmacy, Peking University First Hospital, Beijing, China

    Xiaocong Pang

  7. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China

    Dongyuan Chang

  8. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China

    Xinan Sheng

  9. Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Qian Zhang

  10. Drug Clinical Trial institution, Peking University First Hospital, Beijing, China

    Yu Fan

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Contributions

Y.F., Q.Z., and Y.M. conceived and designed the study. Y.M., Y. Chen, Y. Cui, and X.S. contributed to sample acquisition. Y.M., Y.T. and K.Y. performed experiments and collected clinical data. Q.S. and Y.M. interpreted, organized, and analyzed the experimental results. Y.F., Q.Z. and X.S. provided overall supervision. Y.M. and Q.S. drafted the manuscript. Y.F., Q.Z., Z.H., W.Y., X.P. and D.C. provided manuscript guidance and critical revisions. Y.F., Q.Z. and X.S. provided funding support and submission guidance. All authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Xinan Sheng, Qian Zhang or Yu Fan.

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The authors declare no competing interests.

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The experiments involved in this study were approved by the Ethics Committee of Peking University First Hospital with exemption from informed consent (2023-289-001). All methods were performed in accordance with the relevant guidelines and regulations.

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Mulati, Y., Shen, Q., Chen, Y. et al. Systematic profiling of tumor-associated antigen expression for antibody-drug conjugate in prostate cancer. Prostate Cancer Prostatic Dis (2025). https://doi.org/10.1038/s41391-025-01066-4

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