Clinically Actionable Tumor-Associated Antigens in Prostate Cancer

Expression Profiles And Prognostic Implications Of Clinically Actionable Tumor-Associated Antigens Across Diverse Clinicopathological Subtypes of Prostate Cancer: a Bidirectional Cohort Study

The goal of this observational study is to evaluate and validate the expression and prognostic value of 15 ADC-targetable membrane proteins (PSMA, B7-H3, STEAP1, TROP2, KLK2, HER2, TF, HER3, DLL3, SEZ6, STEAP2, MUC1, NECTIN4, FAP, PDL1) in patients with diverse clinicopathological subtypes of prostate cancer (e.g. primary and different metastatic types，HSPC and CRPC， PC with neuroendocrine differentiation, cribriform/intraductal carcinoma).

The main questions it aims to answer are:

1. What is the expression profile of 15 clinically actionable targes in tumor tissues from patients with diverse clinicopathological subtypes of prostate cancer?
2. Can the prognostic value of these targets (e.g. association with overall survival) identified in a retrospective cohort be validated in an independent prospective cohort? Researchers will head-to-head compare the expression levels among different targets and across different disease stages/metastatic site. Researchers will also assess whether the targets showing prognostic significance in the retrospective cohort can also predict survival outcomes in the prospective cohort.

Participants in the retrospective cohort have already provided archived tissue samples and clinical data. Participants in the prospective cohort (metastatic prostate cancer patients) will be invited to provide residual tumor tissue samples obtained during standard care and will be followed up regularly for clinical outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; Metastatic Prostate Cancer; Metastatic Prostate Cancer (mCRPC)
• Intervention / Treatment: Other: Immunohistochemistry (IHC) Staining and Analysis

Detailed Description

1. Study Type This is a single-center, observational cohort study incorporating both retrospective and prospective components. It is a non-interventional study that does not involve assignment of participants to specific interventions.
2. Objectives

Primary Objectives:

1. To determine the protein expression profile (positive rate, expression level) of 15 membrane targets (PSMA, B7-H3, STEAP1, TROP2, KLK2, HER2, TF, HER3, DLL3, SEZ6, STEAP2, MUC1, NECTIN4, FAP, PDL1) in diverse clinicopathological subtypes of prostate cancer (HSPC and CRPC，primary and metastatic lesions include lymph node, bone and visceral metastasis, etc.).
2. To characterize the molecular subtypes of prostate cancer based on the expression profiles of AR, PSA, PSMA, Syn, CgA, CD56, p53, RB1, and PTEN across different disease states and metastatic sites.
3. To validate the association between the expression of prognostically significant targets (identified in the retrospective cohort) and overall survival (OS) in an independent, prospectively enrolled cohort of prostate cancer patients.

Secondary Objectives:

1. To compare the expression of each target between matched CSPC and mCRPC samples from the same patients.
2. To compare the expression of each target across different metastatic sites (e.g., bone, lymph node, viscera) in mCRPC.
3. To analyze the association between target expression and clinical outcomes [biochemical recurrence-free survival (BFS), metastasis-free survival (MFS)] in patients with CSPC.
4. To explore co-expression patterns of the targets and their correlation with clinicopathological features.

3.Study Design

Retrospective Cohort:

Population: Patients treated at Peking University First Hospital between 2000-2022.

Cohort 1: Primary Tumor Cohort - This cohort includes patients with CSPC or CRPC, or those with special pathological structures, for whom primary tumor tissue (from biopsy or surgery) is available.

Cohort 2: Lymph Node Metastasis Cohort - This cohort includes patients with CSPC or CRPC for whom lymph node metastasis tissue is available (from biopsy or surgery) .

Cohort 3: Bone Metastasis Cohort - This cohort includes patients with CSPC or CRPC, for whom bone metastasis tissue is available (from biopsy or surgery).

Cohort 4: Visceral Metastasis Cohort - This cohort includes patients with CSPC or CRPC, for whom visceral (e.g., liver, lung) metastasis tissue is available.

Procedures: Archived FFPE tissue blocks will be retrieved for immunohistochemistry (IHC) staining. Clinical and follow-up data will be extracted from medical records.

Prospective Cohort:

Population: Newly diagnosed metastatic prostate cancer patients at Peking University First Hospital from January 1, 2026.

Cohort 5: Prospective Validation Cohort - This cohort will consist of patients with metastatic prostate cancer (mHSPC or mCRPC), from whom tissue samples will be collected prospectively along with their clinical data.

Procedures: Eligible patients will provide informed consent. Residual tumor tissue obtained during standard-of-care biopsies or surgeries will be collected for IHC staining. Patients will be followed prospectively at defined intervals to collect treatment and outcome data.

4.Methods Laboratory Assessment (for both cohorts): IHC will be performed on FFPE tissue sections using validated antibodies against the eight targets (as specified in the protocol: e.g., HER2: ab2142275; TROP2: ab214488; etc.). Staining will be evaluated by pathologists blinded to clinical outcomes. IHC score 0-3,0=negative/none,1=weak,2=moderate,3=strong. A modified H-score ([1×% weak staining + 2×% moderate staining + 3×% strong staining], range 0-300) will be used for quantification.

Data Collection: Clinical data (demographics, laboratory assessment (tPSA、LDH levels)，imaging data(ultrasound, MRI, CT, PET, providing TNM staging results, treatment history, pathology reports) and outcome data (biochemical recurrence, metastasis, death) will be collected retrospectively from databases/records for the retrospective cohort and prospectively during follow-up visits for the prospective cohort.

• Study Type: Observational
• Enrollment (Estimated): 1600

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1. Retrospective Cohorts: These four groups are defined by the origin of the archived tumor tissue specimen at Peking University First Hospital (2000-2025). Each cohort includes patients across the spectrum of disease states (castration-sensitive [CSPC] and castration-resistant [CRPC] prostate cancer) and those with special clinicopathological subtypes (e.g., neuroendocrine differentiation, cribriform/intraductal carcinoma).
2. Prospective Validation Cohort: This group will consist of patients with metastatic prostate cancer recruited at Peking University First Hospital starting January 1, 2026. Participants will provide informed consent for the use of residual tumor tissue (from any anatomic site) obtained during standard clinical care and for prospective clinical follow-up.

The core material for analysis is formalin-fixed, paraffin-embedded (FFPE) tumor tissue from all participants, which will be subjected to immunohistochemical (IHC) staining for biomarker evaluation.

Description

Inclusion Criteria:

• For the Retrospective Cohorts (mCRPC, CSPC, Special Pathology):

  1. Patients with a pathological diagnosis of prostate cancer.
  2. Treated at Peking University First Hospital between January 2000 and 2025.
  3. Availability of adequate, qualified formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks for research.
  4. Availability of essential clinical and follow-up data in medical records.

• For the Prospective Cohort:

  1. Age ≥ 18 years.
  2. CSPC, primarily includes patients who underwent neoadjuvant therapy and have paired pre- and post-treatment biopsy and surgical specimens; or patients with special clinicopathological subtypes.
  3. metastatic prostate cancer patients.
  4. Planned or recent (within 6 months prior to enrollment) acquisition of tumor tissue (from metastasis or primary site) as part of standard clinical care, with sufficient residual tissue available for the study.
  5. Willing and able to provide written informed consent.

Exclusion Criteria:

• For All Cohorts:

  1. Tumor tissue sample is of insufficient quality or quantity for immunohistochemical (IHC) analysis.
  2. Essential clinical or outcome data are missing or irretrievable, which would preclude meaningful analysis.

• Specifically for the Prospective Cohort:

  1. Any condition that, in the investigator's judgment, would significantly compromise the patient's ability to provide informed consent or comply with the study follow-up procedures.
  2. Patient refusal to participate.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Primary Tumor Cohort; This retrospective cohort consists of patients with prostate cancer (encompassing castration-sensitive [CSPC], castration-resistant [CRPC] disease states, and those with special clinicopathological subtypes) for whom primary tumor tissue (from biopsy or radical prostatectomy) is available. Archived FFPE specimens were obtained at Peking University First Hospital between 2000 and 2025. This is an observational cohort. No study intervention is administered.	Other: Immunohistochemistry (IHC) Staining and Analysis; Immunohistochemistry staining will be performed on formalin-fixed, paraffin-embedded (FFPE) prostate cancer tissue sections to quantitatively assess the expression levels of eight membrane protein targets: PSMA, HER2, TROP2, NECTIN4, DLL3, STEAP1, B7-H3, and PDL1. This is a laboratory-based biomarker analysis and does not constitute a therapeutic intervention for participants.
Lymph Node Metastasis Cohort; This retrospective cohort consists of patients with prostate cancer (encompassing CSPC, CRPC disease states, and those with special clinicopathological subtypes) for whom lymph node metastasis tissue is available. Archived FFPE specimens were obtained at Peking University First Hospital between 2000 and 2025. This is an observational cohort. No study intervention is administered.	Other: Immunohistochemistry (IHC) Staining and Analysis; Immunohistochemistry staining will be performed on formalin-fixed, paraffin-embedded (FFPE) prostate cancer tissue sections to quantitatively assess the expression levels of eight membrane protein targets: PSMA, HER2, TROP2, NECTIN4, DLL3, STEAP1, B7-H3, and PDL1. This is a laboratory-based biomarker analysis and does not constitute a therapeutic intervention for participants.
Bone Metastasis Cohort; This retrospective cohort consists of patients with prostate cancer (encompassing CSPC, CRPC disease states, and those with special clinicopathological subtypes) for whom bone metastasis tissue is available. Archived FFPE specimens were obtained at Peking University First Hospital between 2000 and 2025. This is an observational cohort. No study intervention is administered.	Other: Immunohistochemistry (IHC) Staining and Analysis; Immunohistochemistry staining will be performed on formalin-fixed, paraffin-embedded (FFPE) prostate cancer tissue sections to quantitatively assess the expression levels of eight membrane protein targets: PSMA, HER2, TROP2, NECTIN4, DLL3, STEAP1, B7-H3, and PDL1. This is a laboratory-based biomarker analysis and does not constitute a therapeutic intervention for participants.
Visceral Metastasis Cohort; This retrospective cohort consists of patients with prostate cancer (encompassing CSPC, CRPC disease states, and those with special clinicopathological subtypes) for whom visceral metastasis (e.g., liver, lung) tissue is available. Archived FFPE specimens were obtained at Peking University First Hospital between 2000 and 2025. This is an observational cohort. No study intervention is administered.	Other: Immunohistochemistry (IHC) Staining and Analysis; Immunohistochemistry staining will be performed on formalin-fixed, paraffin-embedded (FFPE) prostate cancer tissue sections to quantitatively assess the expression levels of eight membrane protein targets: PSMA, HER2, TROP2, NECTIN4, DLL3, STEAP1, B7-H3, and PDL1. This is a laboratory-based biomarker analysis and does not constitute a therapeutic intervention for participants.
Prospective Validation Cohort; This is a prospective, observational cohort. It will enroll metastatic prostate cancer patients (mHSPC or mCRPC) at Peking University First Hospital starting January 1, 2026. Participants will provide informed consent. Residual tumor tissue (from any site) obtained during standard-of-care procedures will be collected for biomarker analysis, and participants will be followed prospectively for clinical outcomes. No study intervention is administered.	Other: Immunohistochemistry (IHC) Staining and Analysis; Immunohistochemistry staining will be performed on formalin-fixed, paraffin-embedded (FFPE) prostate cancer tissue sections to quantitatively assess the expression levels of eight membrane protein targets: PSMA, HER2, TROP2, NECTIN4, DLL3, STEAP1, B7-H3, and PDL1. This is a laboratory-based biomarker analysis and does not constitute a therapeutic intervention for participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression Profile in the Retrospective Prostate Cancer Cohort	The protein expression profiles of 15 tumor-associated antigens (PSMA, B7-H3, STEAP1, TROP2, KLK2, HER2, TF, HER3, DLL3, SEZ6, STEAP2, MUC1, NECTIN4, FAP, PDL1) and molecular subtype markers (AR, PSA, Syn, CgA, CD56, p53, RB1, and PTEN) in tumor tissues from the four retrospective site-based cohorts (Primary Tumor, Lymph Node Metastasis, Bone Metastasis, Visceral Metastasis). Measure: Expression level assessed by IHC score (0-3) , modified H-score (0-300) (positive expression defined as a H-score > 20) for each target within each cohort.	Baseline (at time of metastatic site sample acquisition)
Validation in the Prospective Cohort	The association between the expression status (positive/negative or H-score level) of prognostically significant ADC targets (identified in the retrospective cohort) and Overall Survival (OS) in the prospectively enrolled mCRPC validation cohort. This is a confirmatory analysis. Measure: Hazard Ratio (HR) with 95% Confidence Interval (CI) from Cox proportional hazards model.	From date of prospective cohort enrollment until death from any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target Expression Difference: Primary Tumor vs. Paired Metastasis	The difference in expression level (IHC score or H-score) for each target between primary tumor and matched metastasis (from any site) from the same patients, where such paired samples are available in the retrospective cohorts. Measure: IHC score or H-score.	Baseline (at time of matched sample acquisition)
Target Expression Difference: Across Different Metastatic Sites	The difference in expression level (IHC score or H-score) for each target among the different metastatic sites (Lymph Node, Bone, Viscera) in the retrospective cohorts. Measure: IHC score or H-score.	Baseline
Target Expression in Special Clinicopathological Subtypes (Subgroup Analysis)	The expression profile of the 15 tumor-associated antigens in tumor tissues with neuroendocrine differentiation or cribriform/intraductal carcinoma (CF/IDC), analyzed as a subgroup across retrospective cohorts. Measure: IHC score or H-score.	Baseline
Prognostic Association in Retrospective Prostate Cancer Cohort	The association between tumor-associated antigens expression status and clinical outcomes in the retrospective retrospective prostate cancer cohort, with sub-analysis by disease state (CSPC vs. CRPC). Measure: Hazard Ratios (HR) for Metastasis-free Survival (MFS) and (for CSPC sub-group) Biochemical Recurrence-free Survival (BFS).	From date of radical prostatectomy until biochemical recurrence, metastasis, or death, assessed up to 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-expression and Complementary Expression Patterns of ADC Targets	Exploration of co-expression patterns among the 15 tumor-associated antigens and their correlation with clinicopathological features. Characterization of molecular subtypes based on expression profiles of key markers (e.g., AR, Syn, etc.) across different anatomic sites and disease states	Baseline

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: mCRPC; ADC; NEPC; CSPC
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques; Histocytological Preparation Techniques; Immunohistochemistry; Staining and Labeling
• Other Study ID Numbers: 2022CR16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No