Table 2.

miRNAs and their potential as biomarkers of cholangiopathies.

Cholangiopathy	Source	miRNA	Clinical Correlation	Human	Reference
CCA
	1. Bile samples from patients who underwent prognostic and/or therapeutic bile drainage	Sensitivity level of 88.9% miR-9 miR-302c miR-199a-3p miR-222 Largest Area under ROC-curve: miR-9 and miR-145 Most promising miR: miR-9	Diagnosis	Bile samples from patients with CCA (cholangiocarcinoma n = 7, gall bladder cancer n = 2) Bile samples from patients with choledocholithiasis without malignancy or inflammatory condition (age-matched) (n = 9)	[100]
	2. Surgical specimens of ICC (chemo and radiotherapy naïve)	Overexpressed in ICC compared to control: miR-21 miR-31 miR-223 Down-regulated in ICC compared to control: miR-122 miR-145 miR-146a miR-200c miR-221 miR-222	No correlation found with clinicopathological features but encouraged further prospective studies to explore the significance of findings	Surgical specimens of ICC (n = 21) Liver specimens of healthy controls (n = 98)	[102]
	3. Surgical specimens of CCA (chemo and radiotherapy naïve)	Higher expression correlated with worse prognosis: miR-21	Prognosis	Surgical specimens of CCA (n = 41)	[104]
	4. Surgical specimens of CCA	Concordant dysregulation: miR-151-3p miR-126	Prognosis and potential therapeutic targets	Surgical specimens of CCA with adjacent uninvolved bile duct epithelium (n = 32)	[103]
	5. Bile samples obtained during ERCP or PTC	miR-species panel: miR-191 miR-486-3p miR-1274b miR-16 miR-484	Diagnosis	Bile samples obtained during ERCP from CCA patients (n = 46) Controls (n = 50)	[49]
	6. Tumor tissue from liver fluke (Opisthorchis Vierrini) (Ov)—associated cholangiocarcinoma and serum	miR significantly higher in the serum of CCA patients compared to healthy subjects: miR-192	Prognosis and diagnosis	Tumor with adjacent non-tumor tissues (n = 30) Sera from patients with ICC (n=51) Sera from healthy subjects negative for Ov (n = 32) Sera from subjects infected with Ov (n = 10) Subjects with periductal fibrosis (n = 20)	[101]
	7. Plasma from patients with Ov induced ICC	Detected in ICC but not control: miR-483-5p miR-505-3p miR-874 miR-885-5p miR-320b miR-92b-3p miR-1275 miR-1307-3p	Diagnosis	Plasma samples of Ov-induced ICC from patients: Well differentiated ICC (n = 4) Moderately differentiated ICC (n = 2) Papillary ICC (n = 6) Plasma controls (n = 5)	[105]
PLD
	1. Urine specimens of ADPKD patients	Higher in urine cells from ADPKD compared to other chronic kidney disease (CKD) patients: miR-143(2) Lower in urine cells from APKD compared to other CKD patients: miR-133b(2) miR-1(4) Increased abundance in ADPKD urine cells: miR-223(1) miR-199a(3) miR-199b(1) Less abundant in ADPKD urine microvesicles compared to other CKD patients miR-1(2) miR-133a(2)	Monitoring disease progression and treatment response	Urine specimens of ADPKD patients (n = 20) Urine specimens of patients with CKD of other etiologies (n = 20)	[106]
PBC
	1. Serum from patients with PBC	Downregulated in PBC: hsa-miR-505-3p miR-197-3p	Diagnosis	Sera of patients with PBC (n = 10) (treatment naïve), sera of patients with CH-B (n = 5), sera of patients with CH-C (n = 5), and sera of healthy controls (n = 5).	[107]
	2. Peripheral blood mononuclear cells (PBMCs) from PBC patients	Upregulated in PBC: miR-15a-5p miR-20a-5p miR-140-3p miR-106b-5p Down-regulated in PBC: miR-3654 miR-181a-5p	Diagnosis or treatment	PBC patients (n = 9) and healthy controls (n = 9) matched by gender and age	[108]
	3. Serum from patients with PBC	Upregulated in PBC: hsa-miR-122-5p hsa-miR-34a-5p hsa-miR-141-3p hsa-miR-27b-3p Downregulated in PBC: hsa-miR-26b-5p	Diagnosis	Sera of patients with PBC (n = 207) Sera of healthy controls (n = 173)	[109]
BA
	1. Serum	Upregulated in BA: miR-200b/429	Diagnosis		[110]

ICC: Intrahepatic Cholangiocarcinoma; ERCP: Endoscopic Retrograde Cholangiopancreatography; PTC: Percutaneous Transhepatic Cholangiography; OV: Opisthorchis Vierrini; PLD: Polycystic Liver Disease; ADPKD: Autosomal dominant polycystic kidney disease; PBC: Primary biliary cirrhosis; CH-B: chronic hepatitis B; CH-C: chronic hepatitis C; BA: Biliary atresia.