A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy

McKiernan, James M.; Donovan, Michael; O’Neill, Vincent; Bentink, Stefan; Noerholm, Mikkel; Belzer, Susan; Skog, Johan; Kattan, Michael W.; Partin, Alan W.; Andriole, Gerald L.; Brown, Gordon A.; Wei, John T.; Thompson, Ian M.; Carroll, Peter R.

doi:10.1001/jamaoncol.2016.0097

Cited by 537 publications

(445 citation statements)

References 57 publications

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“…Surprisingly, no prostasomes (MVs) were present in urine from PCa patients, while no exosomes were found in the urine of healthy donors, possibly due to the increased biogenesis of exosomes in the maligned tissue. In another study, mRNAs of ERG (including TMPRSS2: ERG), PCA3, and SPDEF in urine exosomes plus standard of care (SOC), which includes prostate-specific antigen (PSA) level, age, race, and family history, were found to more accurately discriminate PCa with Gleason scores higher than 7 from lower grade PCa or benign lesions (209). Combination of exosomal RNA analysis with SOC increased the value of receiver operating characteristic curve (AUC) to 0.77, compared to 0.66 for SOC alone and 0.61 for PSA alone.…”

Section: Translational Applications Of Evs In Cancermentioning

confidence: 99%

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

Xing

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

126

115

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Extracellular vesicles (EVs) have emerged as important players of cancer initiation and progression through cell-cell communication. They have been recognized as critical mediators of extracellular communications, which promote transformation, growth invasion, and drug-resistance of cancer cells. Interestingly, the secretion and uptake of EVs are regulated in a more controlled manner than previously anticipated. EVs are classified into three groups, (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on their sizes and origins, and novel technologies to isolate and distinguish these EVs are evolving. The biologically functional molecules harbored in these EVs, including nucleic acids, lipids, and proteins, have been shown to induce key signaling pathways in both tumor and tumor microenvironment (TME) cells for exacerbating tumor development. While tumor cell-derived EVs are capable of reprogramming stromal cells to generate a proper tumor cell niche, stromal-derived EVs profoundly affect the growth, resistance, and stem cell properties of tumor cells. This review summarizes and discusses these reciprocal communications through EVs in different types of cancers. Further understanding of the patcment of tumor specific therapeutics. This review will also discuss the translational aspects of EVs and therapeutic opportunities of utilizing EVs in different cancer types.

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Section: Translational Applications Of Evs In Cancermentioning

confidence: 99%

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

Xing

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

126

115

View full text Add to dashboard Cite

show abstract

“…A urinary 3-gene expression assay in exosomes has demonstrated an improved identification of patients with higher-grade prostate cancer among men with elevated PSA reduce the number of unnecessary biopsies Fig. 2 Exosomes promote cell-cell communication playing an important role in gene regulation due to their ability to transport cancerpromoting material such as miRNAs [69]. In a proof-of-concept study analyzing the transcriptome in tumor exosomes isolated from the urine of patients with prostate cancer, revealed biomarkers, with potential for monitoring cancer patients.…”

Section: Exosomes and Prostasomesmentioning

confidence: 99%

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

et al. 2017

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Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cellderived extracellular vesicles such as exosomes. Exosomes have been shown to act as mediators for cell to cell communication because of the regulatory functions of their content. High levels of exosomes are found in several body fluids from cancer patients and could be a potential source of non-invasive biomarkers. In this review, we summarize the diagnostic and prognostic utility of exosomal miRNAs in prostate cancer.

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“…With a negative predictive value of 97.5% within "gray zone" serum, PSA in the 2-10 ng/mL range EXO106 score has emerged as a promising tool to aid initial biopsy decision-making [42]. Exosome gene expression assay was then externally validated in the prospective, multisite trial under the name ExoDx Prostate Intelliscore [34,116]. With expression levels cut-points set in training cohort, 27% biopsies in independent "gray zone" cohort would have been avoided, missing only 5% of patients with HGPCa.…”

Section: Will Urine Exosome Assays Reduce the Number Of Unnecessary Bmentioning

confidence: 99%

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

Zapała

Dybowski²,

Poletajew³

et al. 2017

Urol Int

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Along with significant advances in prostate cancer biology research, we also observe the rapid development of modern diagnostic tests. New biomarkers are derived to detect disease while it is organ-confined to stratify the risk and to aid clinical decision-making. Majority of these tools have already been validated clinically, but only a few have received premarket clearance and administration approval. Superiority of novel tests is visible not only in improved detection accuracy but predominantly in the assessment of tumour aggressiveness and selection of patients eligible for conservative management. Two factors limiting the clinical implementation of validated biomarker candidates are costs and local availability. For these reasons, currently, their true clinical role starts after routine screening with prostate-specific antigen test. With this review of prostate cancer biomarkers, we attempted to draw general conclusions on clinical perspectives of these novel tools.

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A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy

Cited by 537 publications

References 57 publications

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

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