Emerging Role of microRNA Dysregulation in Diagnosis and Prognosis of Extrahepatic Cholangiocarcinoma.

Extrahepatic cholangiocarcinomas, also called bile duct carcinomas, represent a special entity in gastrointestinal tumors, and histological specimens of the tumors are often difficult to obtain. A special feature of these tumors is the strong neovascularization, which can often be seen in the endoluminal endoscopic procedure called cholangioscopy, performed alone or in combination with laserscanning techniques. The additional analysis of microRNA expression profiles associated with inflammation and neovascularization in bile duct tumors or just the bile duct fluid of these patients could be of enormous additional importance. In particular, the dysregulation of microRNA in these cholangiocarcinomas (CCA) was previously reported to affect epigenetics (reported for miR-148, miR-152), inflammation (determined for miR-200, miR-125, and miR-605), and chemoresistance (miR-200b, 204) in patients with cholangiocarcinoma. More importantly, in the context of malignant neovascularization, well-defined microRNAs including miR-141, miR-181, miR-191, and miR-200b have been found to be dysregulated in cholangiocarcinoma and have been associated with an increased proliferation and vascularization in CCA. Thus, a panel of these microRNA molecules together with the clinical aspects of these tumors might facilitate tumor diagnosis and early treatment. To our knowledge, this is the first review that outlines the unique potential of combining macroscopic findings from cholangioscopy with microRNA expression.

MicroRNAs as Indicators of Malignancy in Pancreatic Ductal Adenocarcinoma (PDAC) and Cystic Pancreatic Lesions.

The dysregulation of microRNAs has recently been associated with cancer development and progression in pancreatic ductal adenocarcinoma (PDAC) and cystic pancreatic lesions. In solid pancreatic tumor tissue, the dysregulation of miR-146, miR-196a/b, miR-198, miR-217, miR-409, and miR-490, as well as miR-1290 has been investigated in tumor biopsies of patients with PDAC and was reported to predict cancer presence. However, the value of the predictive biomarkers may further be increased during clinical conditions suggesting cancer development such as hyperinsulinemia or onset of diabetes. In this specific context, the dysregulation of miR-486 and miR-196 in tumors has been observed in the tumor tissue of PDAC patients with newly diagnosed diabetes mellitus. Moreover, miR-1256 is dysregulated in pancreatic cancer, possibly due to the interaction with long non-coding RNA molecules that seem to affect cell-cycle control and diabetes manifestation in PDAC patients, and, thus, these three markers may be of special or "sentinel value". In blood samples, Next-generation sequencing (NGS) has also identified a set of microRNAs (miR-20a, miR-31-5p, miR-24, miR-25, miR-99a, miR-185, and miR-191) that seem to differentiate patients with pancreatic cancer remarkably from healthy controls, but limited data exist in this context regarding the prediction of cancer presences and outcomes. In contrast to solid pancreatic tumors, in cystic pancreatic cancer lesions, as well as premalignant lesions (such as intraductal papillary neoplasia (IPMN) or mucinous-cystic adenomatous cysts (MCAC)), the dysregulation of a completely different expression panel of miR-31-5p, miR-483-5p, miR-99a-5p, and miR-375 has been found to be of high clinical value in differentiating benign from malignant lesions. Interestingly, signal transduction pathways associated with miR-dysregulation seem to be entirely different in patients with pancreatic cysts when compared to PDAC. Overall, the determination of these different dysregulation "panels" in solid tumors, pancreatic cysts, obtained via fine-needle aspirate biopsies and/or in blood samples at the onset or during the treatment of pancreatic diseases, seems to be a reasonable candidate approach for predicting cancer presence, cancer development, and even therapy responses.