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A Non-invasive Liquid Biopsy Screening of Urine-Derived Exosomes for miRNAs as Biomarkers in Endometrial Cancer Patients

The AAPS Journal volume 20, Article number: 82 (2018) Cite this article

Abstract

Exosomes have great potential to serve as a source of diagnostic and prognostic biomarkers for endometrial cancer (EC). Urine-derived exosomes from patients with EC and patients with symptoms of EC, but without established EC, were used to evaluate a unique miRNA expression profile. Of the 84 miRNA studied, 57 were amplified in qPCR, suggesting the differential packaging of miRNA in exosomes. Further, hsa-miR-200c-3p was identified to be enriched the most. Various bioinformatics and in silico tools were used to evaluate the biological significance of hsa-miR-200c-3p in EC. We conclude that differential miRNA in exosomes can be utilized for discovery of biomarker signatures and EC diagnosis; hsa-miR-200c-3p is one such candidate. Urine-derived exosomes pave the way for the development of non-invasive biomarkers.

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Acknowledgements

The authors thank all the patients for providing the samples and the dedicated cancer center staff for assistance in sample collection. Editorial assistance from Ms. Kathy Kyler at the office of Vice President of Research, OUHSC, is appreciated. Rajagopal Ramesh is an Oklahoma TSET Research Scholar and holds the Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics.

Funding

The work was supported in part by funds received from the Stephenson Cancer Center Seed Grant (RR), Presbyterian Health Foundation Seed Grant (RR), Presbyterian Health Foundation Bridge Grant (RR), Chapman Foundation, and Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics (RR) at the University of Oklahoma Health Sciences Center.

Author information

Author notes

  1. Akhil Srivastava, Katherine Moxley and Rachel Ruskin contributed equally to this work.

Affiliations

  1. Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Akhil Srivastava & Rajagopal Ramesh

  2. Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Akhil Srivastava, Katherine Moxley, Rachel Ruskin, Danny Natarajan Dhanasekaran, Yan Daniel Zhao & Rajagopal Ramesh

  3. Department of Gynecology Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Katherine Moxley & Rachel Ruskin

  4. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Danny Natarajan Dhanasekaran

  5. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Yan Daniel Zhao

  6. Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Rajagopal Ramesh

  7. Department of Pathology, Stanton L. Young Biomedical Research Center, Suite 1403, 975 N.E., 10th Street, Oklahoma City, Oklahoma, 73104, USA

    Rajagopal Ramesh

Authors
  1. Akhil Srivastava
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  2. Katherine Moxley
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  3. Rachel Ruskin
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  4. Danny Natarajan Dhanasekaran
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  5. Yan Daniel Zhao
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Contributions

AS, KM, and RR conducted the studies and collected data; YDZ performed statistical analysis; AS, KM, RR, DND, YDZ, and RR conceived and designed the studies; AS and RR wrote the manuscript; AS, KM, RR, DND, YDZ, and RR critically analyzed and interpreted the data; AS, KM, RR, DND, YDZ, and RR critically reviewed, provided suggestions, and edited the manuscript; and RR supervised the project.

Corresponding author

Correspondence to Rajagopal Ramesh.

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The authors declare that they have no conflict of interest.

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Guest Editors: Juliane Nguyen and Steven Jay

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Srivastava, A., Moxley, K., Ruskin, R. et al. A Non-invasive Liquid Biopsy Screening of Urine-Derived Exosomes for miRNAs as Biomarkers in Endometrial Cancer Patients. AAPS J 20, 82 (2018). https://doi.org/10.1208/s12248-018-0220-y

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KEY WORDS

  • exosomes
  • endometrial cancer
  • miRNA
  • liquid biopsy
  • biomarkers