Copyright ©The Author(s) 2020.
World J Gastrointest Surg. Oct 27, 2020; 12(10): 407-424
Published online Oct 27, 2020. doi: 10.4240/wjgs.v12.i10.407
Table 1 Potential clinical application of selected extracellular vesicle-derived microRNAs as biomarkers in cholangiocarcinoma
microRNAExpression Type of EVsEV source Major finding Potential applicationRef.
miR-205Exosomes Human CCA cell linesDownregulation of miR-205-5p decreased migration and invasion in CCA cell linesTherapy monitoring/therapeutic target[47]
Members of miR-200 family
miR-200c-3p, miR-200b-3p, miR-200a-3p, miR-429 and miR-141-3pExosomesHuman CCA cell lines Supported the role of exosomal miR-200 family in CCA progressionPrognostic value[47]
miR-200c-3p, miR-200a/c-3p ExosomesPeripheral blood samples (36 patients)(a) miR-200c-3p emerged as a potential diagnostic biomarker; and (b) miR-200a/c-3p emerged as a potential diagnostic and prognostic biomarkerEarly diagnostic and prognostic value[48]
miR-199 familyExosomesHuman CCA cell linesSupported the role of miR-199 family in CCA carcinogenesis-[47]
miR-214ExosomesHuman CCA cell linesSupported the role of miR-214 in CCA carcinogenesis-[47]
5 miR-based panel (miR-191, miR-486-3p, miR-1274b, miR-16 and miR-484)EVsBile samples (46 CCA vs 50 control patients with PSC, biliary obstruction and bile leak)(a) The panel displayed a 67% sensitivity and 96% specificity for CCA diagnosis; and (b) tool for differential diagnosis between biliary obstruction of nonmalignant etiologies and CAADiagnostic value[49]
miR-30eEVsNonmalignant human cell vs CCA cell linesEncapsulation of miR-30e in EVs could suppress CCA cell invasion and migration by inhibiting EMTEVs may be used as vehicles for delivery of therapeutic agents[50]
miR-195EVsHuman liver stellate cell lineCoculture of CCA and stellate cell lines resulted in downregulation of miR-195. EV-mediated miR-195 transfer targeted tumor cells and inhibited proliferation in a rat model.EVs may be used as vehicles for delivery of therapeutic agents[52]
miR-604EVsSerumDisplayed 0.944 diagnostic capacity for CCADiagnostic value[53]
miR-551BEVsSerumDisplayed 0.909 diagnostic capacity for CCADiagnostic value[53]
miR-96-5p, miR-151a-5p, miR-191-5p and miR-4732-3pExosomesBloodStage II CCA patients displayed the highest levelsDiagnostic value in early CCA stages[58]
miR-9-5pExosomesHuman ICC samplesSignificant association with malignancy promotion via ↑IL-6 expression in vCAFsPrognostic value[59]
Table 2 Potential clinical application of selected extracellular vesicle-derived long noncoding RNAs as biomarkers in cholangiocarcinoma
lncRNAExpressionType of EVsEV sourceMajor findingPotential applicationRef.
ENST00000517758.1 and ENST00000588480.1ExosomesBile samples of CCA (n = 35) and biliary obstruction patients (n = 56)(a) ENST00000588480.1 expression may contribute to tumorigenesis and CCA progression (via p53 signaling pathway); and (b) Combined ENST00000588480.1 and ENST00000517758.1 exhibited higher sensitivity than CA19-9 (82.9% vs 74.3%)Diagnostic value; Prognostic value/Therapeutic target[63]
MALAT-1EVsSerumUpregulated in EVs from CCA vs PSC patientsDiagnostic value[53]