Startseite Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance
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Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance

  • Jan Dominik Kuhlmann EMAIL logo , Issam Chebouti , Rainer Kimmig , Paul Buderath , Michael Reuter , Sven-Holger Puppel , Pauline Wimberger und Sabine Kasimir-Bauer
Veröffentlicht/Copyright: 13. November 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 57 Heft 7

Abstract

Background

Extracellular vesicle (EV)-associated microRNAs (miRNAs) have been suggested as promising biomarkers for blood-based cancer diagnosis. However, one of the major limitations for the use of EVs with diagnostic purpose is the lack of standardized EV-profiling techniques. In this regard, the objective of our study was to design an integrated next-generation sequencing (NGS)-based workflow for analyzing the signature of EV-associated miRNA in the plasma of platinum-resistant ovarian cancer patients.

Methods

For EV-extraction, different enrichment methods were compared (ExoQuick vs. exoRNeasy). NGS was performed with the Illumina platform.

Results

We established an integrated NGS-based workflow, including EV-enrichment with the ExoQuick system, which resulted in an optimal RNA-yield and consistent small RNA libraries. We applied this workflow in a pilot cohort of clinically documented platinum-sensitive (n=15) vs. platinum-resistant (n=15) ovarian cancer patients, resulting in a panel of mature EV-associated miRNAs (including ovarian cancer associated miR-181a, miR-1908, miR-21, miR-486 and miR-223), which were differentially abundant in the plasma of platinum-resistant patients.

Conclusions

This is the first study, analyzing the profile of EV-associated miRNAs in platinum-resistant ovarian cancer patients. We provide rationale to further validate these miRNA candidates in an independent set of patients, in order to characterize their biomarker potential as predictors for platinum-resistance.

Keywords: extracellular vesicles; microRNAs; next-generation-sequencing; ovarian cancer; platinum-resistance
Corresponding author: Dr. Jan Dominik Kuhlmann, Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany, Phone: +49-351-458-2434, Fax: +49-351-458-5844

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was funded by “VFK Krebsforschung gGmbH”.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-1048).

Received: 2018-09-24
Accepted: 2018-10-09
Published Online: 2018-11-13
Published in Print: 2019-06-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Epigenetics in cancer: a promising path to follow?
  4. Reviews
  5. The circulating miRNAs as diagnostic and prognostic markers
  6. Analytical barriers in clinical B-type natriuretic peptide measurement and the promising analytical methods based on mass spectrometry technology
  7. Mini Review
  8. Commutability of reference and control materials: an essential factor for assuring the quality of measurements in Laboratory Medicine
  9. EFLM Paper
  10. Preanalytical challenges – time for solutions
  11. General Clinical Chemistry and Laboratory Medicine
  12. Iron status determination in individuals with Helicobacter pylori infection: conventional vs. new laboratory biomarkers
  13. Harmonizing by reducing inter-run variability: performance evaluation of a quality assurance program for antinuclear antibody detection by indirect immunofluorescence
  14. Increased prevalence of anti-DFS70 antibodies in young females: experience from a large international multi-center study on blood donors
  15. Accuracy of determination of the glomerular filtration marker iohexol by European laboratories as monitored by external quality assessment
  16. Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU): new preanalytic aspects
  17. Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels
  18. Hematology and Coagulation
  19. Determination of haemoglobin derivatives in aged dried blood spot to estimate haematocrit
  20. Reference Values and Biological Variations
  21. A study of biological and lifestyle factors, including within-subject variation, affecting concentrations of growth differentiation factor 15 in serum
  22. Reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in elderly Chinese persons
  23. Cancer Diagnostics
  24. Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance
  25. Evaluating the diagnostic and prognostic value of serum long non-coding RNA CTC-497E21.4 in gastric cancer
  26. A pilot study of new promising non-coding RNA diagnostic biomarkers for early-stage colorectal cancers
  27. Cardiovascular Diseases
  28. Prognostic role of GDF-15 across the spectrum of clinical risk in patients with NSTE-ACS
  29. Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction
  30. Diabetes
  31. Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio
  32. Letters to the Editor
  33. The search for a new test of early cancer detection
  34. Need of a dedicated isotopic internal standard for accurate 3-epi-25(OH)D3 quantification by LC-MS/MS
  35. An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?
  36. Creatine kinase elevation: a neglected clue to the diagnosis of polymyositis. A case report
  37. Analytical performance of the new Siemens NT-proBNP assays on the Advia Centaur XPT compared to the NT-proBNP method on the Dimension Vista
  38. Free PAPP-A as a biomarker: heparin-induced release is not related to coronary atherosclerotic burden
  39. Anti-citrullinated protein antibodies are not associated with extent of disease or prognosis in patients with coronary artery disease
  40. A new preanalytical factor: conveyor transport influences residual platelet concentrations
  41. Stability of cannabinoids in cannabis FM1 flowering tops and oil preparation evaluated by ultra-high performance liquid chromatography tandem mass spectrometry
  42. Requirement of a reference measurement system for the tissue factor-induced coagulation time and the international normalized ratio
https://doi.org/10.1515/cclm-2018-1048
Schlagwörter für diesen Artikel
extracellular vesicles; microRNAs; next-generation-sequencing; ovarian cancer; platinum-resistance

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Epigenetics in cancer: a promising path to follow?
  4. Reviews
  5. The circulating miRNAs as diagnostic and prognostic markers
  6. Analytical barriers in clinical B-type natriuretic peptide measurement and the promising analytical methods based on mass spectrometry technology
  7. Mini Review
  8. Commutability of reference and control materials: an essential factor for assuring the quality of measurements in Laboratory Medicine
  9. EFLM Paper
  10. Preanalytical challenges – time for solutions
  11. General Clinical Chemistry and Laboratory Medicine
  12. Iron status determination in individuals with Helicobacter pylori infection: conventional vs. new laboratory biomarkers
  13. Harmonizing by reducing inter-run variability: performance evaluation of a quality assurance program for antinuclear antibody detection by indirect immunofluorescence
  14. Increased prevalence of anti-DFS70 antibodies in young females: experience from a large international multi-center study on blood donors
  15. Accuracy of determination of the glomerular filtration marker iohexol by European laboratories as monitored by external quality assessment
  16. Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU): new preanalytic aspects
  17. Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels
  18. Hematology and Coagulation
  19. Determination of haemoglobin derivatives in aged dried blood spot to estimate haematocrit
  20. Reference Values and Biological Variations
  21. A study of biological and lifestyle factors, including within-subject variation, affecting concentrations of growth differentiation factor 15 in serum
  22. Reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in elderly Chinese persons
  23. Cancer Diagnostics
  24. Extracellular vesicle-associated miRNAs in ovarian cancer – design of an integrated NGS-based workflow for the identification of blood-based biomarkers for platinum-resistance
  25. Evaluating the diagnostic and prognostic value of serum long non-coding RNA CTC-497E21.4 in gastric cancer
  26. A pilot study of new promising non-coding RNA diagnostic biomarkers for early-stage colorectal cancers
  27. Cardiovascular Diseases
  28. Prognostic role of GDF-15 across the spectrum of clinical risk in patients with NSTE-ACS
  29. Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction
  30. Diabetes
  31. Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio
  32. Letters to the Editor
  33. The search for a new test of early cancer detection
  34. Need of a dedicated isotopic internal standard for accurate 3-epi-25(OH)D3 quantification by LC-MS/MS
  35. An unexpectedly prolonged severe hyperbilirubinemia in a patient with pre-existing hepatitis A: a role of genetic predisposition?
  36. Creatine kinase elevation: a neglected clue to the diagnosis of polymyositis. A case report
  37. Analytical performance of the new Siemens NT-proBNP assays on the Advia Centaur XPT compared to the NT-proBNP method on the Dimension Vista
  38. Free PAPP-A as a biomarker: heparin-induced release is not related to coronary atherosclerotic burden
  39. Anti-citrullinated protein antibodies are not associated with extent of disease or prognosis in patients with coronary artery disease
  40. A new preanalytical factor: conveyor transport influences residual platelet concentrations
  41. Stability of cannabinoids in cannabis FM1 flowering tops and oil preparation evaluated by ultra-high performance liquid chromatography tandem mass spectrometry
  42. Requirement of a reference measurement system for the tissue factor-induced coagulation time and the international normalized ratio
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