Circulating plasma levels of MicroRNA-21 and MicroRNA-221 are potential diagnostic markers for primary intrahepatic cholangiocarcinoma Journal Article


Authors: Correa-Gallego, C.; Maddalo, D.; Doussot, A.; Kemeny, N.; Kingham, T. P.; Allen, P. J.; D'Angelica, M. I.; DeMatteo, R. P.; Betel, D.; Klimstra, D.; Jarnagin, W. R.; Ventura, A.
Article Title: Circulating plasma levels of MicroRNA-21 and MicroRNA-221 are potential diagnostic markers for primary intrahepatic cholangiocarcinoma
Abstract: Background: MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression in intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with potential diagnostic and prognostic utility. Methods: Using deep-sequencing techniques, miRNA expression between tumor samples and non-neoplastic liver parenchyma were compared. Overexpressed miRNAs were measured in plasma from an independent cohort of patients with cholangiocarcinoma using RT-qPCR and compared with that healthy volunteers. The discriminatory ability of the evaluated plasma miRNAs between patients and controls was evaluated with receiving operating characteristic (ROC) curves. Results: Small RNAs from 12 ICC and 11 tumor-free liver samples were evaluated. Unsupervised hierarchical clustering using the miRNA expression data showed clear grouping of ICC vs. non-neoplastic liver parenchyma. We identified 134 down-regulated and 128 upregulated miRNAs. Based on overexpression and high fold-change, miR21, miR200b, miR221, and miR34c were measured in plasma from an independent cohort of patients with ICC (n = 25) and healthy controls (n = 7). Significant overexpression of miR-21 and miR-221 was found in plasma from ICC patients. Furthermore, circulating miR-21 demonstrated a high discriminatory ability between patients with ICC and healthy controls (AUC: 0.94). Conclusion: Among the differentially expressed miRNAs in ICC, miR-21 and miR-221 are overexpressed and detectable in the circulation. Plasma expression levels of these miRNAs, particularly miR-21, accurately differentiates patients with ICC from healthy controls and could potentially serve as adjuncts in diagnosis. Prospective validation and comparison with other hepatobiliary malignancies is required to establish their potential role as diagnostic and prognostic biomarkers. © 2016 Correa-Gallego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 11
Issue: 9
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2016-09-29
Start Page: e0163699
Language: English
DOI: 10.1371/journal.pone.0163699
PROVIDER: scopus
PMCID: PMC5042503
PUBMED: 27685844
DOI/URL:
Notes: Article -- Export Date: 2 November 2016 -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. David S Klimstra
    978 Klimstra
  3. Peter Allen
    501 Allen
  4. William R Jarnagin
    903 Jarnagin
  5. T Peter Kingham
    609 Kingham
  6. Andrea Ventura
    56 Ventura
  7. Nancy Kemeny
    543 Kemeny
  8. Juan Camilo Correa
    30 Correa
  9. Alexandre Florent Doussot
    15 Doussot