Liquid Biopsy in Diagnosis and Prognosis of Non-Metastatic Prostate Cancer

Abstract

Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.

Detection and Molecular Characterization of Circulating Tumour Cells: Challenges for the Clinical Setting

“…High-risk non-metastatic PCa has the potential to progress into lethal disease since it remains unclear which treatment offers the best results. However, diagnosis and prognosis of non-metastatic prostate cancer patients could gain another perspective by applying molecular tests to peripheral blood [ 59 ]. Moreover, the detection and molecular characterization of CTCs can lead to a promising strategy for monitoring MRD or relapses following local therapy.…”

Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer

“…Growing evidence suggests that metastatic progression is mediated by exosomal microRNAs, short non-coding RNA sequences that can regulate post-transcriptional gene expression [44]. Aberrant expression of various specific miRNAs has been observed in several tumors, including breast [46], lung [47], colorectal cancer [85], ovarian [86], and prostate cancer [16,87]. Exosomal miRNA has indeed served as a potential useful biomarker in several human malignancies for better distinguishing tumor tissue from normal tissue, classifying tumor origin, and understanding tumor staging [16,88].…”

“…Aberrant expression of various specific miRNAs has been observed in several tumors, including breast [46], lung [47], colorectal cancer [85], ovarian [86], and prostate cancer [16,87]. Exosomal miRNA has indeed served as a potential useful biomarker in several human malignancies for better distinguishing tumor tissue from normal tissue, classifying tumor origin, and understanding tumor staging [16,88]. Mechanistically, microRNAs mediate the crosstalk between tumor cells and the TME to regulate tumor growth [89].…”

“…These exosomal miRNAs affect cancer progression by reducing apoptosis, increasing proliferation, migration, adhesion of cancer cells [90][91][92], and regulating the phenotypic epithelial-mesenchymal transition (EMT) of prostate cancer cells [93]. These miRNAs also contribute to ADT resistance by creating a TME enabling tumor cell proliferation, differentiation, and angiogenesis and recruiting fibroblasts and immune cells [16].…”

“…EVs contain molecular footprints from their cell of origin [2], including lipids, proteins, metabolites, RNA, and DNA [6][7][8][9][10][11]13,14]. They are present in almost all types of cells and have been successfully isolated from blood, urine, semen, and other body fluids [15][16][17]. EVs have been widely studied for their role in the tumor microenvironment (TME) and cancer progression and metastasis, specifically their involvement in cell-to-cell communication via vesicle trafficking, molecular targeting and intricate delivery mechanism [4,12,18,19].…”