Diagnostic utility of quantitative analysis of microRNA in bile samples obtained during endoscopic retrograde cholangiopancreatography for malignant biliary strictures

Abstract

Background The sensitivity of bile cytology for malignant biliary strictures is not adequate. To overcome this limitation, we evaluated whether quantitative analysis of microRNAs (miRNAs) in bile can provide a precise diagnosis of malignant biliary strictures due to pancreatic cancer (PC) and biliary tract cancer (BTC). Methods This was a retrospective evaluation of miRNA levels in stored bile samples of patients with PC, BTC or benign biliary stricture obtained during biliary drainage from April 2019 to December 2021 at our institution. A total of 113 patients (PC; n = 40, BTC; n = 38, control; n = 35) were enrolled. The miRNA candidates to be quantified were determined with microarray analysis from each 3 patients with PC, BTC and controls. Results Using microarray analysis, we confirmed four significantly up-regulated miRNAs (miR-1275, miR-6891-5p, miR-7107-5p, miR-3197) in patients with PC and BTC compared to control patients. Quantitative PCR was then performed in 113 bile samples for these miRNAs. miR-1275 was significantly upregulated in PC (p = 0.003) and BTC (p = 0.049) compared to controls, miR-6891-5p was significantly upregulated in PC compared to controls (p = 0.025). In particular, a combination of bile cytology and miR-1275 in bile showed a sensitivity of 77.5% (95% CI, 70.7–77.5%), specificity of 100% (95% CI, 92.2–100%) and an area under the curve (AUC) of 0.93, and provided a significantly greater additional diagnostic effect than bile cytology alone (p = 0.014). Conclusions This study suggest that bile miRNAs could be potential biomarkers for pancreato-biliary diseases, particularly miR-1275 and miR-6891-5p may be helpful in the diagnosis of PC and BTC.

Identification of survival related key genes and long-term survival specific differentially expressed genes related key miRNA network of primary glioblastoma

“…These studies are listed as follows: miR-6512-3p has ability as a sponge with genes such as CYTOR, SNHG7 and HOTTIP [ [33] , [34] , [35] ]. miR-6817-3p stabilizes Wnt2B through the mechanism of ceRNA combined with AC104041.1, thereby exerting anticancer effects [ 36 ]; miR-6833-3p regulates the tumorigenesis effect of colorectal through the LINC-ROR/miR-6833-3p/SMC4 axis [ 37 ]; miR-6809-3p, miR-6829-3p, and miR-6804-5p are one of the miRs targeting overexpressed genes in lung cancer [ 38 ]; miR-7107-5p and miR-6891-5p are one of the markers identified in endoscopic cholangiopancreatography for the treatment of bile in malignant biliary strictures [ 39 ]; miR-1910-3p in exosomes activates NF-kB pathway through MTMR3 to promote proliferation, metastasis and autophagy in breast cancer [ 40 ]; The miR198-CUL4B pathway mediates circMFN2 induced glycolysis in ovarian cancer and has sensitization effect in gemcitabine treatment of pancreatic cancer [ 41 , 42 ]; miR-4446-3p was found in the serum of colon adenocarcinoma patients and has diagnostic value [ 43 ]; miR-6894-5p promotes gastric cancer progression through the activation of circAFF2 [ 44 ]; miR-6794-5p participates in constructing a large-scale microRNA map detection model for esophageal squamous cell carcinoma [ 45 ]; miR-197-5p adsorbed by circ0125803 in glioblastoma can lead to tumor progression and it increases the anticancer cytotoxicity of HT1080 fibrosarcoma cells mediated by doxorubicin by reducing drug efflux [ 46 , 47 ]; miR-6795-5p is an important component of LINC01013-miR-6795-5p-FMNL3 axis regulation of liver cancer stem cell characteristics [ 48 ]; miR-3154 is one of the potential prognostic biomarkers for cervical cancer and it is one of the potential prognostic biomarkers for cervical cancer [ 49 , 50 ]; miR-936 mediates cell proliferation and invasion in glioma through the miR-936/ERBB4 axis and it mediate the acquisition of non androgen dependent prostate cancer metastasis phenotype when it lossed. It also targeting GPR78 to regulate chemotherapy resistance in non-small cell lung cancer [ 51 ]; Down regulation of lincRNA DSCR9 delays breast cancer progression by regulating microRNA-504-5p-dependent G-protein-coupled receptor 65 [ 52 ]; The content of miR-6127 significantly increased in extracellular vesicles of metastatic colorectal cancer cell lines intervened by rapamycin [ 53 ]; EWI-2, located on the cell membrane and extracellular vesicles of miR-3934-5p, is a key molecule that regulates the distribution of miR-3934-5p and has the function of inhibiting prostate cancer cell metastasis [ 54 ].…”