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Updated: Jun 29, 2025
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Impact of Circulating Tumor Cell-Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen
Hyungseok Cho1, Seok-Soo Byun2, Nak-Hoon Son3
1Department of Nanoscience and Engineering Center for Nano Manufacturing, Inje University, Gimhae, South Korea.
Purpose:
Prostate-specific membrane antigen (PSMA)-based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)-based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer.
Experimental Design:
We prospectively enrolled 21 healthy individuals and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]. The mRNA expression of six transcripts [PSMA, prostate-specific antigen (PSA), AR, AR-V7, EpCAM, and KRT 19] from CTCs was measured, and their relationship with biochemical recurrence (BCR) in LPCa and mCRPC progression-free survival (PFS) rate in mHSPC was assessed. PSA-PFS and radiological-PFS were also calculated to identify potential biomarkers for predicting androgen receptor signaling inhibitor (ARSI) and taxane-based chemotherapy resistance in mCRPC.
Results:
CTC detection rates were 75.5%, 95.3%, and 98.0% for LPCa, mHSPC, and mCRPC, respectively. In LPCa, PSMA [hazard ratio (HR), 3.35; P = 0.028) and PSA mRNA (HR, 1.42; P = 0.047] expressions were associated with BCR. Patients with mHSPC with high PSMA (HR, 4.26; P = 0.020) and PSA mRNA (HR, 3.52; P = 0.042) expressions showed significantly worse mCRPC-PFS rates than those with low expression. Increased PSA and PSMA mRNA expressions were significantly associated with shorter PSA-PFS and radiological PFS in mCPRC, indicating an association with drug resistance.
Conclusions:
PSMA and PSA mRNA expressions are associated with BCR in LPCa. In advanced prostate cancer, PSMA and PSA mRNA can also predict rapid progression from mHSPC to mCRPC and ARSI or taxane-based chemotherapy resistance.
Insights
Prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) mRNA from circulating tumor cells (CTCs) can predict prostate cancer recurrence and progression. High PSMA and PSA mRNA levels indicate a higher risk of treatment resistance in advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Prostate-specific membrane antigen (PSMA) imaging quantifies PSMA expression for detecting prostate cancer micrometastases.
- Circulating tumor cell (CTC) analysis offers a minimally invasive approach to molecular profiling in cancer.
Purpose of the Study:
- To evaluate a CTC-based transcript platform, including PSMA mRNA, for identifying prognostic markers in prostate cancer.
- To assess the utility of PSMA and other mRNA transcripts in CTCs for predicting treatment outcomes.
Main Methods:
- Prospective enrollment of 247 prostate cancer patients (localized, hormone-sensitive metastatic, castration-resistant metastatic) and 21 healthy individuals.
- Measurement of mRNA expression for PSMA, PSA, AR, AR-V7, EpCAM, and KRT 19 from CTCs.
- Correlation of mRNA expression with biochemical recurrence (BCR) in localized prostate cancer and progression-free survival (PFS) in metastatic disease.
Main Results:
- High detection rates of CTCs across all prostate cancer stages (75.5% to 98.0%).
- PSMA and PSA mRNA expression in CTCs significantly associated with BCR in localized prostate cancer.
- Elevated PSMA and PSA mRNA levels in CTCs correlated with worse progression-free survival and predicted resistance to androgen receptor signaling inhibitors and taxane-based chemotherapy in advanced prostate cancer.
Conclusions:
- PSMA and PSA mRNA expression in CTCs serve as valuable biomarkers for predicting BCR in localized prostate cancer.
- These mRNA markers can predict disease progression and chemotherapy resistance in advanced prostate cancer, aiding in treatment selection and monitoring.
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