miRNA Panel for PCa Diagnosis
Efficacy Exploration of Non-Invasive Diagnostic Strategies for Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) Based on Body Fluid miRNA Panels: A Prospective Diagnostic Study
This is a single-center, prospective diagnostic accuracy trial conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine, led by a team of urology and molecular medicine researchers. A total of 500 male participants aged 18 years or older who meet clinical indications for prostate biopsy will be enrolled between May 2026 and May 2027. All participants have suspected prostate cancer (PCa) based on abnormal prostate-specific antigen (PSA), abnormal digital rectal examination (DRE), suspicious multiparametric MRI (mpMRI), positive family history of prostate cancer, pathogenic gene mutations, or other high-risk clinical findings. Men with confirmed treated prostate cancer, recent prostate-related procedures, active other malignancies, severe organ dysfunction, coagulation disorders, or cognitive impairment that prevents informed consent will be excluded.
The core goal of this study is to test the diagnostic performance of a novel non-invasive blood test using a panel of circulating microRNAs (miRNAs) from serum, and compare it with the standard PSA-based screening tools to distinguish prostate cancer from benign prostatic hyperplasia (BPH). The gold standard for judging true disease status will be pathology results from transrectal ultrasound-guided prostate biopsy. Researchers will calculate key diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC) for the miRNA panel. Secondary analyses will evaluate whether combining the miRNA signature with PSA or mpMRI improves diagnostic accuracy, especially for men with PSA levels in the ambiguous "gray zone" of 4-10 ng/mL. Subgroup assessments will also test how well the miRNA panel differentiates low-risk versus high-risk prostate cancer and clinically significant versus insignificant tumors across different PSA tiers, age groups, mpMRI risk scores and prostate sizes. Additional laboratory testing will confirm the stability of serum miRNAs under different storage temperatures and storage durations, as well as test consistency across operators, reagent batches and detection platforms to validate real-world clinical usability.
For participants, the study only involves a one-time fasting venous blood draw of up to 10 mL before biopsy, with no extra invasive procedures or experimental medications added to routine clinical care. The free miRNA test results can serve as supplementary evidence to help doctors judge whether a prostate biopsy is truly necessary, potentially sparing many patients from unnecessary invasive biopsy and its associated discomfort or complications. All blood samples will be stored under standardized biosafety protocols with de-identified personal data to fully protect participant privacy. Minimal risks include minor temporary bruising or slight pain at the blood draw site, which resolve spontaneously without long-term harm.
Statistical analysis will use three defined datasets (full analysis set, per-protocol set, safety set) and advanced methods including DeLong's test, logistic regression, NRI and IDI to quantify diagnostic improvement versus PSA. A 70% training cohort will build the miRNA diagnostic model, and the remaining 30% of samples will act as an independent validation group to verify model reliability. Safety monitoring will record all adverse events throughout follow-up, with strict ethical oversight following the Declaration of Helsinki and Chinese biomedical research regulations. After sample testing, data analysis and result summarization finish by October 2027, the research team plans to publish 1-2 peer-reviewed SCI papers to share findings globally. If validated, this serum miRNA panel will provide a more precise, non-invasive screening tool to reduce overdiagnosis and unnecessary prostate biopsies, optimize early prostate cancer detection, and lower overall medical burdens for men at risk of prostate disease in clinical practice.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Wei Xue, Phd
- Phone Number: 8621-58752345
- Email: uroxuewei@163.com
Study Locations
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Shanghai, China, 200127
- Recruiting
- Renji Hospital Shanghai Jiao Tong University School of Medicine
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Contact:
- Wei Xue, Phd
- Phone Number: 8621-58752345
- Email: uroxuewei@163.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
Male participants aged ≥18 years Serum PSA > 4.0 ng/mL confirmed by repeat testing with ≥4-week interval, excluding interfering conditions such as acute urinary retention, catheterization and prostatitis PSA within gray zone (4.0-10.0 ng/mL) accompanied by abnormal f/t PSA ratio <0.16, PSAD >0.15 ng/mL/g or PSAV >0.75 ng/mL/year Persistently rising PSA on two consecutive tests with abnormal PSAV regardless of absolute PSA value Abnormal digital rectal examination (DRE): palpable hard, nodular, fixed or asymmetric prostate lesions, indistinct induration or suspected space-occupying lesions Suspicious transrectal ultrasound (TRUS): hypoechoic nodules, hypervascular areas or disrupted prostatic capsule mpMRI PI-RADS v2.1 score ≥3, especially lesions scoring 4-5 Elevated focal PSMA uptake on PSMA PET/CT (if performed) First-degree relative with prostate cancer and personal PSA >3.0 ng/mL Carriers of pathogenic BRCA1/2, HOXB13 mutations with PSA >3.0 ng/mL Prior negative prostate biopsy with subsequent sustained PSA elevation or new suspicious mpMRI lesions Unexplained bone pain or pathological fracture with elevated PSA requiring exclusion of primary prostate malignancy Aggravated bladder outlet obstruction with elevated PSA or abnormal DRE requiring differentiation of malignant obstruction
Exclusion Criteria:
Confirmed prostate cancer receiving radical surgery, radiotherapy, androgen deprivation therapy or active surveillance Acute bacterial prostatitis, febrile urinary tract infection or acute urinary retention within the preceding 4 weeks Prostate massage, cystoscopy, ejaculation within 72 hours; prostate biopsy within 6 weeks; transurethral prostate surgery within 3 months prior to screening Active concurrent malignancy or history of any malignant tumor within the past 5 years (non-melanoma skin cancer excluded) Severe Child-Pugh grade C liver dysfunction, eGFR <30 mL/min/1.73m², coagulopathy (INR >1.5 or platelet count <50×10⁹/L) Unable to discontinue anticoagulants (warfarin, dabigatran, rivaroxaban) or dual antiplatelet therapy for ≥5 days Severe cognitive impairment or acute psychiatric disorder precluding independent informed consent, follow-up and biospecimen collection Participation in other interventional clinical trials within 3 months or concurrent observational trials interfering with study outcomes Hematological disorders including myelodysplastic syndrome and leukemia that alter serum nucleic acid stability Severe peripheral vascular disease hindering venipuncture or inability to comply with fasting blood collection requirements
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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PCa cohort
Two diagnostic subgroups classified by histopathological gold standard from prostate biopsy: Cohort 1: Participants diagnosed with prostate cancer (PCa) Cohort 2: Participants diagnosed with benign prostatic hyperplasia (BPH) and other non-malignant prostate lesions All 500 enrolled subjects originate from a single unified screening cohort of men with suspected prostate lesions meeting biopsy indications; post-biopsy pathological results allocate subjects into the above two analytical cohorts. |
This diagnostic test quantitatively detects a custom panel of circulating microRNAs (miRNAs) extracted from fasting serum specimens collected from participants within 24 hours prior to transrectal ultrasound-guided prostate biopsy.
Total RNA is isolated from serum samples, reverse-transcribed into cDNA, and quantified via quantitative real-time PCR (qRT-PCR).
The miRNA expression signature is used to construct a logistic regression/machine learning diagnostic model, whose discriminatory performance is benchmarked against total PSA, f/t PSA ratio, and multiparametric MRI (mpMRI).
Unique aspects of this test include: 1) systematic evaluation of miRNA stability under varied serum storage temperatures and storage durations; 2) assessment of inter-operator, inter-batch reagent, and inter-platform assay reproducibility via coefficient of variation (CV); 3) stratified performance testing across PSA gray zone (4-10 ng/mL), ISUP low/high-risk prostate cancer subgrou
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BPH cohort
Two diagnostic subgroups classified by histopathological gold standard from prostate biopsy: Cohort 1: Participants diagnosed with prostate cancer (PCa) Cohort 2: Participants diagnosed with benign prostatic hyperplasia (BPH) and other non-malignant prostate lesions All 500 enrolled subjects originate from a single unified screening cohort of men with suspected prostate lesions meeting biopsy indications; post-biopsy pathological results allocate subjects into the above two analytical cohorts. |
This diagnostic test quantitatively detects a custom panel of circulating microRNAs (miRNAs) extracted from fasting serum specimens collected from participants within 24 hours prior to transrectal ultrasound-guided prostate biopsy.
Total RNA is isolated from serum samples, reverse-transcribed into cDNA, and quantified via quantitative real-time PCR (qRT-PCR).
The miRNA expression signature is used to construct a logistic regression/machine learning diagnostic model, whose discriminatory performance is benchmarked against total PSA, f/t PSA ratio, and multiparametric MRI (mpMRI).
Unique aspects of this test include: 1) systematic evaluation of miRNA stability under varied serum storage temperatures and storage durations; 2) assessment of inter-operator, inter-batch reagent, and inter-platform assay reproducibility via coefficient of variation (CV); 3) stratified performance testing across PSA gray zone (4-10 ng/mL), ISUP low/high-risk prostate cancer subgrou
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Area under the receiver operating characteristic curve (AUC) of serum miRNA panel for differentiating prostate cancer from benign prostatic hyperplasia
Time Frame: Completed after pathological diagnosis results of prostate biopsy are available for all enrolled participants, following serum miRNA laboratory testing and statistical analysis of the full study cohort.
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Evaluate the AUC, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum miRNA signature using transrectal ultrasound-guided prostate biopsy pathology as the diagnostic gold standard.
Compare the miRNA panel's diagnostic performance against serum total PSA via DeLong test.
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Completed after pathological diagnosis results of prostate biopsy are available for all enrolled participants, following serum miRNA laboratory testing and statistical analysis of the full study cohort.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Incremental diagnostic benefit of serum miRNA panel combined with PSA or mpMRI; stratified diagnostic performance across PSA subgroups and prostate cancer risk tiers
Time Frame: After completion of all biopsy pathology reports, serum miRNA testing and stratified subgroup statistical analyses of the full 500-subject cohort
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1. Compare diagnostic gain of miRNA panel vs total PSA and f/t PSA via NRI and IDI; assess combined miRNA-PSA/mpMRI model accuracy especially for PSA gray zone (4-10 ng/mL).
2. Evaluate panel performance stability in PSA <4, 4-10, >10 ng/mL strata; distinguish low-risk (ISUP 1-2) vs high-risk (ISUP 3-5) and clinically significant/insignificant prostate cancer.
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After completion of all biopsy pathology reports, serum miRNA testing and stratified subgroup statistical analyses of the full 500-subject cohort
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Assay reproducibility and serum miRNA stability under different sample storage conditions
Time Frame: Concurrent with batch serum miRNA laboratory testing throughout participant enrollment and sample processing phase
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Calculate coefficient of variation (CV) across different operators, reagent batches and detection platforms.
Detect miRNA expression changes in serum stored at room temperature, 4°C and -80°C over variable storage durations to verify clinical laboratory suitability.
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Concurrent with batch serum miRNA laboratory testing throughout participant enrollment and sample processing phase
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wei Xue, PhD, RenJi Hospital
- Principal Investigator: Pengfei Wang, MD, RenJi Hospital
- Principal Investigator: Liang Dong, PhD, RenJi Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- LY2026-105-B
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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