Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research

Abstract

Prostate cancer is a global cancer burden and considerable effort has been made through the years to identify biomarkers for the disease. Approximately a decade ago, the potential of analysing extracellular vesicles in liquid biopsies started to be envisaged. This was the beginning of a new exciting area of research investigating the rich molecular treasure found in extracellular vesicles to identify biomarkers for a variety of diseases. Vesicles released from prostate cancer cells and cells of the tumour microenvironment carry molecular information about the disease that can be analysed in several biological fluids. Numerous studies document the interest of researchers in this field of research. However, methodological issues such as the isolation of vesicles have been challenging. Remarkably, novel technologies, including those based on nanotechnology, show promise for the further development and clinical use of extracellular vesicles as liquid biomarkers. Development of biomarkers is a long and complicated process, and there are still not many biomarkers based on extracellular vesicles in clinical use. However, the knowledge acquired during the last decade constitutes a solid basis for the future development of liquid biopsy tests for prostate cancer. These are urgently needed to bring prostate cancer treatment to the next level in precision medicine.

Machine learning diagnosis by immunoglobulinN‐glycan signatures for precision diagnosis of urological diseases

“…Although several promising biomarkers have been reported for early detection of urological diseases using miRNAs and exosomes. [7][8][9][10] there is only one report on diagnostic Ig N-glycan signatures of urological diseases. 3 Glycomics is a new subspecialty in omics science and holds great promise as a next-generation biomarker for precision medicine.…”

“…Several techniques that use miRNAs and exosomes for early diagnosis of urological diseases have been reported. [7][8][9][10] N-glycosylation is also a promising target for the detection. 2,4,[11][12][13][14] Previously, we focused on aberrant N-glycosylation of Ig, one of the major serum proteins, and found an aberrant N-glycan signature of Ig using capillary electrophoresis-based N-glycomics, and suggested it might be useful for diagnosing BCa and UTUC.…”

“…Several techniques that use miRNAs and exosomes for early diagnosis of urological diseases have been reported 7–10 . N ‐glycosylation is also a promising target for the detection 2,4,11–14 .…”

Exploration of Extracellular Vesicle miRNAs, Targeted mRNAs and Pathways in Prostate Cancer: Relation to Disease Status and Progression

“…As 80%, on average, of the targets were expressed in any EV sample (Table S13), we restricted our analysis to mRNAs expressed in at least a 5-fold higher level in the primary patient EV samples than in the post-RP sample of P33, thereby attempting to focus on detectable transcripts from prostate, PCa or metastasis. As positive controls for this strategy, we checked the expression of SPDEF, a known uEV biomarker with roles in PCa initiation and progression [47] and TGM4, detected in uEV with enriched expression in prostate and PCa tissues and correlated with unfavourable prognosis [19,48]. The expression of SPDEF and TGM4 mRNA were >5-fold higher in all three primary PCa patient uEV samples, relative to the post-RP uEV sample (Table S4).…”

“…Equally little is known regarding whether analysis of miRNA with their target mRNA from EV adds valuable insights into PCa pathogenesis, or how EV from urine and plasma differ in their RNA cargo. These are interesting questions because, along with their own challenges, both sample types also have unique potential in PCa research and diagnostics, e.g., urine as a source of EV from primary tumour and blood as a source of EV from distant metastasis [19].…”