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Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
Published on: January 3, 2013
B7-H3 and c-MET in advanced prostate cancer: exploring possibilities of novel bi-specific drug development
Weiying He1, Huiyu Li2, Wenjia Sun1
1Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.116 Zhuodaoquan South Road, Wuhan, 430079, Hubei, China.
Purpose:
Prostate cancer (PCa) is a serious malignancy worldwide with the fifth highest mortality rate among tumors in males, and there are unmet clinical needs for PCa treatment. In this work, we aim to explore the expression and overlap between B7 Homolog 3 protein (B7-H3) and cell-surface receptor c-mesenchymal-epithelial transition factor (c-MET), to provide insight on B7-H3 and c-MET bi-specific ADC drugs development for advanced PCa.
Patients And Methods:
In this retrospective cross-sectional study, formalin-fixed paraffin-embedded (FFPE) samples were analyzed from 135 male patients with advanced PCa at Hubei Cancer Hospital between 2019 and 2023. Biomarker and drug information were collected and used as major factors for patient stratification. Protein expression of B7-H3 (D9M2L) and c-MET (SP44) were determined by staining intensity and percent staining measurements. Positive expression of B7-H3 was defined as H Score ≥100, and positive expression of c-MET was defined as H Score >0. Historical medical information related to these cases were collected and the data were analyzed by R.
Results:
44% samples had both positive B7-H3 expression and c-MET expression, but c-MET expression is higher in peri-tumor sites than it in tumor site in PCa. The expression of B7-H3 and c-MET did not demonstrate significant correlation with age, metastatic site, or disease control rate (DCR). In addition, progression-free survival (PFS) of B7-H3 negative c-MET positive group was significantly shorter compared to the rest groups in patients receiving androgen deprivation therapy (ADT), while the expression of two markers was not significantly correlated with PFS in patients receiving ADT and new androgen receptor (AR) antagonists.
Conclusions:
In conclusion, B7-H3 is a promising drug developing target for PCa; however, c-MET may be limited by its low expression in tumor site while relative higher expression in peri-tumor site in PCa. Further investigation is warranted regarding bi-specific drugs for B7-H3 and another marker.
Insights
B7-H3 shows promise as a prostate cancer (PCa) therapeutic target. While co-expression with c-MET occurs, c-MET
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Prostate cancer (PCa) presents significant global mortality and unmet treatment needs.
- B7 Homolog 3 protein (B7-H3) and c-MET are emerging targets in cancer therapy.
Purpose of the Study:
- To investigate the expression patterns and overlap of B7-H3 and c-MET in advanced PCa.
- To inform the development of bi-specific antibody-drug conjugates (ADCs) targeting B7-H3 and c-MET for PCa treatment.
Main Methods:
- Retrospective analysis of 135 advanced PCa patient samples (2019-2023).
- Protein expression of B7-H3 and c-MET determined via immunohistochemistry (H-score).
- Statistical analysis of biomarker expression correlation with clinical parameters.
Main Results:
- 44% of PCa samples exhibited positive co-expression of B7-H3 and c-MET.
- c-MET expression was higher in peri-tumor regions than in tumor sites.
- B7-H3 negative, c-MET positive patients had shorter progression-free survival (PFS) on androgen deprivation therapy (ADT).
Conclusions:
- B7-H3 is a promising therapeutic target for advanced PCa.
- c-MET's utility may be limited by its tumor site expression profile.
- Further research into bi-specific agents targeting B7-H3 and other markers is warranted.
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