Circulating Plasma Levels of MicroRNA-21 and MicroRNA-221 Are Potential Diagnostic Markers for Primary Intrahepatic Cholangiocarcinoma.
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).


CONCLUSIONS
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.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Camilo
C
Correa-Gallego
Cancer Biology and Genetics Program, Sloan-Kettering Institute, New York, NY, United States of America.
Danilo
D
Maddalo
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Alexandre
A
Doussot
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Nancy
N
Kemeny
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
T Peter
TP
Kingham
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Peter J
PJ
Allen
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Michael I
MI
D'Angelica
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
Ronald P
RP
DeMatteo
Department of Medicine and Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, United States of America.
Doron
D
Betel
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
David
D
Klimstra
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
William R
WR
Jarnagin
Cancer Biology and Genetics Program, Sloan-Kettering Institute, New York, NY, United States of America.
Andrea
A
Ventura
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