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

Abstract

BackgroundMicroRNAs (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.MethodsUsing 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.ResultsSmall 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).ConclusionAmong 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.

Enhanced plasma miR‑142‑5p promotes the progression of intrahepatic cholangiocarcinoma via targeting PTEN

“…Furthermore, miRNAs can be easily detected in small amounts and are resistant to degradation (20,22). These characteristics make miRNAs attractive as potential biomarkers (20). In the present study it was determined that data showed that plasma miR-142-5p was significantly increased in patients with ICC compared with healthy controls.…”

“…It is important to detect ICC early in order to improve treatment outcomes. Increasing evidence has suggested that miRNAs may be used as potential diagnostic biomarkers for ICC and may also serve as therapeutic targets (19,20). miRNAs are able to stably exist in bodily fluids, including serum, plasma, saliva, urine and tears (20,21).…”

“…Increasing evidence has suggested that miRNAs may be used as potential diagnostic biomarkers for ICC and may also serve as therapeutic targets (19,20). miRNAs are able to stably exist in bodily fluids, including serum, plasma, saliva, urine and tears (20,21). Furthermore, miRNAs can be easily detected in small amounts and are resistant to degradation (20,22).…”

“…miRNAs are able to stably exist in bodily fluids, including serum, plasma, saliva, urine and tears (20,21). Furthermore, miRNAs can be easily detected in small amounts and are resistant to degradation (20,22). These characteristics make miRNAs attractive as potential biomarkers (20).…”

Circulating Biomarkers for Cholangiocarcinoma

“…Regarding the use of miRNAs for early detection of CCA, only a few studies of sufficient quality exist to date. In a small cohort of patients, serum levels of miR-21 and miR-221 were found to be significantly elevated in patients with intrahepatic CCA compared to healthy controls (AUC = 0.94) [27]. These findings were corroborated by a different study, showing that circulating levels of miR-21 are able to differentiate between CCA patients and healthy controls (AUC = 0.93) as well as patients with nonmalignant bile duct disease (AUC = 0.83) and decrease after tumor resection [28].…”