Exploring microRNAs as Blood Biomarkers of Pancreatic Cancer

Dr. Murray Korc MD, Professor Department of Medicine, Division of Endocrinology, Biochemistry and Molecular Biology, and the Pancreatic Cancer Signature Center IU Simon Cancer Center, Indiana University School of Medicine Indianapolis, Indiana MedicalResearch.com Interview with
Dr. Murray Korc MD, Professor
Department of Medicine, Division of Endocrinology, Biochemistry and Molecular Biology, and the Pancreatic Cancer Signature Center
IU Simon Cancer Center, Indiana University School of Medicine
Indianapolis, Indiana

Medical Research: What is the background for this study? What are the main findings?

Dr. Korc: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with an overall 5-year survival rate of 6%. Currently, there are no highly specific and sensitive biomarkers in the blood that can be used for definitively diagnosing the presence of this cancer. In addition, in spite of the usefulness of CA19-9 in differentiating between patients with pancreatic cancer and chronic pancreatitis, this test may yield a significant number of false positive and false negative results, and it may be influenced by the presence of jaundice. These difficulties are compounded by the fact that patients with pancreatitis are at-risk for developing Pancreatic ductal adenocarcinoma.

We decided to carry out a study of microRNAs using plasma from treatment-naïve PDAC patients, chronic pancreatitis patients, and controls without pancreatic disease. We focused on microRNAs because they are known to be present in the blood and to be very stable. We chose to conduct these assays in plasma because we reasoned that there would be fewer confounding factors by comparison with either whole blood or serum. We determined that five microRNAs were elevated in plasma from PDAC patients by comparison with either chronic pancreatitis or controls. Importantly, among these five microRNAs, high levels of miR-10b, miR-155, and miR-106b in the plasma were highly accurate in diagnosing Pancreatic ductal adenocarcinoma with ~95% sensitivity and ~100% specificity.

Medical Research: What should clinicians and patients take away from your report?

Dr. Korc: First and foremost, although these are exciting results, clinicians and patients should understand that additional studies are necessary to confirm these findings and explore the utility of this panel as a truly diagnostic test for Pancreatic ductal adenocarcinoma.

Second, a similar miRNA expression profile was observed in bile fluid and pancreatic juice, which may be useful information to gastroenterologists performing diagnostic procedures on patients with bile or pancreatic duct strictures of unknown etiology.

Third, our findings build on existing knowledge in the field generated by hundreds of research laboratories as well as our own laboratory.

Fourth, the study reflects on the joint efforts of clinicians, laboratory investigators, nurses, clinical coordinators, and laboratory technicians, underscoring the importance of team science in the conduct of research with patient-derived samples. Fourth, our findings lend strong support to the concept that microRNAs in the plasma can serve as diagnostic “liquid biopsies” in the management of patients with pancreatic pathologies, especially pancreatic cancer.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Korc: There are many possibilities with respect to future studies that are suggested by the current finding. For example, we should validate the present findings, determine whether these microRNAs can serve as prognostic markers, and evaluate their utility in screening high-risk patients for the presence of early pancreatic cancer.

Citation:

A Pilot Study to Develop a Diagnostic Test for Pancreatic Ductal Adenocarcinoma Based on Differential Expression of Select miRNA in Plasma and Bile
Gregory A Cote MD, MS, A Jesse Gore PhD, Samantha D McElyea MS, Laura E Heathers BA, Huiping Xu PhD, Stuart Sherman MD1 and Murray Korc MD

Am J Gastroenterol advance online publication 28 October 2014; doi: 10.1038/ajg.2014.331