Large-scale Circulating microRNA Profiling for the Liquid Biopsy of Prostate Cancer

Urabe, Fumihiko; Matsuzaki, Juntaro; Yamamoto, Yusuke; Kimura, Takahiro; Hara, Tomohiko; Ichikawa, Makiko; Takizawa, Satoko; Aoki, Yasumichi; Niida, Shumpei; Sanada, Hiromi; Kato, Ken; Egawa, Shin; Fujimoto, Hiroyuki; Ochiya, Takahiro

doi:10.1158/1078-0432.ccr-18-2849

Cited by 91 publications

(77 citation statements)

References 29 publications

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“…Still, studies using PC tissue analyses have implicated miR-33a-5p [41] and miR-409-3p [42] to play a role in bone-metastasis and epithelial-to-mesenchymal transition, respectively. However, a large-scale plasma miRNA profiling study [22], in line with our results, did not detect any difference in plasma levels between miR-33a-5p and miR-409-3p between patients with benign TRUSbx outcomes and patients with LPC. Thus, miRNA expression levels observed in tumor tissue may not fully reflect the expression levels observed in circulation.…”

Section: Discussionsupporting

confidence: 89%

“…Out of the three other miRNAs in bCaP, only miR-16-5p was significantly upregulated in samples from patients with APC, relative to that of samples from patients with BPH or LPC. miR-16-5 has previously displayed elevated expression levels in plasma from LPC patients compared to healthy controls [22,39] as well as elevated expression levels in serum of PC mouse models with bone metastasis [40]. We found no significant changes in expression levels in plasma between samples from BPH or LPC versus APC of either miR-33a-5p or miR-409-3p, indicating that these two miRNAs may simply function as normalization genes in our bCaP model.…”

Section: Discussionmentioning

confidence: 47%

“…In a Japanese study by Urabe et al [22], the authors profiled 2588 miRNAs in >800 plasma samples from non-cancer patients and patients with LPC and found a two-miRNA model consisting of miRNA-17-3p (AUC > 0.91) and miR-1185-2-3p (AUC > 0.92) which, when combined, could detect PC with very high accuracy (AUC > 0.95). In the Urabe dataset, bCaP could not significantly differentiate between non-cancer and LPC patients (AUC = 0.54).…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs are short non-coding RNAs approximately 22 nucleotides in length, which post-transcriptionally regulate gene expression of up to 60% of all human mRNAs and often play a significant role in oncogenesis [13,17,18]. Dysregulation of miRNA expression in PC has previously been demonstrated in both tumor tissue samples and liquid biopsies [19][20][21][22][23][24]. Coupled with the high stability of miRNAs in biofluids [25], this makes them particularly appealing targets as minimally invasive biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Fredsøe

Rasmussen²,

Mouritzen³

et al. 2020

Diagnostics

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Early detection of prostate cancer (PC) is paramount as localized disease is generally curable, while metastatic PC is generally incurable. There is a need for improved, minimally invasive biomarkers as current diagnostic tools are inaccurate, leading to extensive overtreatment while still missing some clinically significant cancers. Consequently, we profiled the expression levels of 92 selected microRNAs by RT-qPCR in plasma samples from 753 patients, representing multiple stages of PC and non-cancer controls. First, we compared plasma miRNA levels in patients with benign prostatic hyperplasia (BPH) or localized prostate cancer (LPC), versus advanced prostate cancer (APC). We identified several dysregulated microRNAs with a large overlap of 59 up/down-regulated microRNAs between BPH versus APC and LPC versus APC. Besides identifying several novel PC-associated dysregulated microRNAs in plasma, we confirmed the previously reported upregulation of miR-375 and downregulation of miR-146a-5p. Next, by randomly splitting our dataset into a training and test set, we identified and successfully validated a novel four microRNA diagnostic ratio model, termed bCaP (miR-375*miR-33a-5p/miR-16-5p*miR-409-3p). Combined in a model with prostate specific antigen (PSA), digital rectal examination status, and age, bCaP predicted the outcomes of transrectal ultrasound (TRUS)-guided biopsies (negative vs. positive) with greater accuracy than PSA alone (Training: area under the curve (AUC), model = 0.84; AUC, PSA = 0.63. Test set: AUC, model = 0.67; AUC, PSA = 0.56). It may be possible in the future to use this simple and minimally invasive bCaP test in combination with existing clinical parameters for a more accurate selection of patients for prostate biopsy.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Fredsøe

Rasmussen²,

Mouritzen³

et al. 2020

Diagnostics

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“…It has been shown that exosome isolation from liquid biopsies improves the sensitivity of miRNA amplification and detection [53]. Cumulating data suggest that miRNAs have potential as diagnostic and/or prognostic biomarkers in PCa [55][56][57][58][59]. Several miRNAs have been studied in plasma and serum of mCRPC patients.…”

Section: Circulating Nucleic Acidsmentioning

confidence: 99%

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies

Boerrigter¹,

Groen

Erp³

et al. 2019

Expert Review of Molecular Diagnostics

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Introduction: Prostate cancer (PCa) is one of the most common malignancies in men and a major cause of cancer deaths among men worldwide. Prostate specific antigen (PSA) monitoring and histopathological examination of tumor biopsies remain gold standards in PCa diagnostics. These clinical parameters are not well suited for patient stratification, predicting and monitoring treatment response. On the other hand, liquid biopsies offer a unique opportunity to easily isolate tumor-derived material for longitudinal clinical assessment. Areas covered: In this review we focus on the clinical application of novel liquid biomarkers that have the potential to monitor and stratify patients in order to achieve better therapeutic effects and improve clinical outcomes. Enumeration and characterization of circulating tumor cells (CTCs), tumor-educated platelets, exosomes, and cell-free nucleic acids have been studied for their clinical utility in PCa diagnostics, prognostics, monitoring treatment response and guiding treatment choice. Expert opinion: Liquid biomarkers have high potential to be used for prognosis, monitoring treatment response and guiding treatment selection. Although there is a remarkable progress in PCa biomarker discovery, their clinical validation is very limited. Research should be focused on biomarker validation and the incorporation of these biomarkers in clinical practice.

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Early prediction of COVID‐19 severity using extracellular vesicle COPB2

Fujita

Hoshina

Matsuzaki

et al. 2021

J of Extracellular Vesicle

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The clinical manifestations of COVID‐19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID‐19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID‐19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID‐19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID‐19 severity. Strikingly, we identified three distinct groups of markers (antiviral response‐related EV proteins, coagulation‐related markers, and liver damage‐related exRNAs) with the potential to serve as early predictive biomarkers for COVID‐19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID‐19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00‐1.00)). The validation set included 40 COVID‐19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73‐0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID‐19 therapy.

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Large-scale Circulating microRNA Profiling for the Liquid Biopsy of Prostate Cancer

Cited by 91 publications

References 29 publications

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Profiling of Circulating microRNAs in Prostate Cancer Reveals Diagnostic Biomarker Potential

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies

Early prediction of COVID‐19 severity using extracellular vesicle COPB2

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