Exploring the circulating biomarkers for prostate cancer progression and treatment monitoring
Abstract
Prostate cancer (PCa) ranks as the second most frequent cancer and the fifth leading cause of cancer death in men worldwide. Androgen-deprivation therapy is the principal treatment for locally advanced and metastatic PCa. However, most patients will progress to castration-resistant PCa (CRPC), which contributes to the majority of PCa deaths. This project aims to investigate the utility of two main types of liquid biopsy, plasma exosomes and circulating tumour cells (CTCs), in monitoring PCa progression and treatment response. We performed RNA-sequencing of plasma exosomal miRNAs in 24 treatmentnaive PCa and 24 CRPC patients and identified different miRNA expression profiles. Several miRNAs were confirmed by reverse transcriptase quantitative polymerase chain reaction in 108 treatment-naive PCa, 42 CRPC and 36 treated non-CRPC patients. The most significantly differentially expressed miRNA, miR-423-3p, was also validated in 30 treatment-naive PCa and 30 CRPC patients at a separate centre. The differentially expressed exosomal miRNAs showed good prediction value for CRPC and showed better prediction value than prostate specific antigen when predicting CRPC from treated non-CRPC. The in vitro study of one miRNA, miR-423-3p, showed that it could enhanced LNCaP cell migration and invasion in hormone-depleted environment. The hormoneindependent subline of LNCaP had higher miR-423-3p expression and increased migration and invasion ability. CTC culture provides a good platform for establishing patient-specific tumour models and study of treatment response. I tested different CTC isolation methods and culture conditions for CTC propagation. Viable CTCs could be isolated from PCa patients’ blood and potentially be propagated in vitro. However, the purity of tumour cells remain low in cultured population and long-term culture remains challenging. This study demonstrated that plasma exosomal miRNAs play important roles in CRPC development and may serve as prediction biomarkers for CRPC occurrence. Long-term culture of PCa CTCs remains challenging and needs further investigation.
Authors
Guo, TianyuCollections
- Theses [4124]