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Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

ABSTRACT: Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid biopsies from 97 patients with PCa. Exo-oncomiR-221-3p, -222-3p and -31-5p were significantly higher in the semen of high-risk patients than in low-risk peers, whereas exo-oncomiR-193-3p and -423-5p were significantly lower in paired samples of post-digital rectal examination urine. A panel of semen biomarkers comprising exo-oncomiR-221-3p, -222-3p and TWEAK was designed that could correctly classify 87.5% of patients with aggressive PCa, with 85.7% specificity and 76.9% sensitivity with an area under the curve of 0.857. We additionally found that TWEAK modulated two exo-oncomiR-221-3p targets, TCF12 and NLK. Overall, we show that liquid biopsy detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis prediction.

SUBMITTER: Ruiz-Plazas X

PROVIDER: S-EPMC7826893 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

Ruiz-Plazas Xavier X Altuna-Coy Antonio A Alves-Santiago Marta M Vila-Barja José J García-Fontgivell Joan Francesc JF Martínez-González Salomé S Segarra-Tomás José J Chacón Matilde R MR

Cancers 20210111 2

Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in po ...[more]

PMID: 33440913

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Project description:Prostate cancer (PCa) is the main cause of cancer-related mortality in males and the diagnosis, treatment, and care of these patients places a great burden on healthcare systems globally. Clinically, PCa is highly heterogeneous, ranging from indolent tumors to highly aggressive disease. In many cases treatment-generally either radiotherapy (RT) or surgery-can be curative. Several key genetic and demographic factors such as age, family history, genetic susceptibility, and race are associated with a high incidence of PCa. While our understanding of PCa, which is mainly based on the tools of molecular biology-has improved dramatically in recent years, efforts to better understand this complex disease have led to the identification of a new type of PCa-oligometastatic PCa. Oligometastatic disease should be considered an individual, heterogeneous entity with distinct metastatic phenotypes and, consequently, wide prognostic variability. In general, patients with oligometastatic disease typically present less biologically aggressive tumors whose metastatic potential is more limited and which are slow-growing. These patients are good candidates for more aggressive treatment approaches. The main aim of the presented review was to evaluate the utility of liquid biopsy for diagnostic purposes in PCa and for use in monitoring disease progression and treatment response, particularly in patients with oligometastatic PCa. Liquid biopsies offer a rapid, non-invasive approach whose use t is expected to play an important role in routine clinical practice to benefit patients. However, more research is needed to resolve the many existing discrepancies with regard to the definition and isolation method for specific biomarkers, as well as the need to determine the most appropriate markers. Consequently, the current priority in this field is to standardize liquid biopsy-based techniques. This review will help to improve understanding of the biology of PCa, particularly the recently defined condition known as "oligometastatic PCa". The presented review of the body of evidence suggests that additional research in molecular biology may help to establish novel treatments for oligometastatic PCa. In the near future, the treatment of PCa will require an interdisciplinary approach involving active cooperation among clinicians, physicians, and biologists.

Dataset Information

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

Publications

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

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