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Study Suggests MicroRNA Panels May Aid in Pancreatic Cancer Diagnoses from Whole Blood Samples

NEW YORK (GenomeWeb News) – A study in the latest issue of the Journal of the American Medical Association suggests that measuring the blood expression levels of particular microRNA panels may bolster the accuracy of nascent non-invasive pancreatic cancer detection schemes.

Danish researchers started by assessing levels of more than 750 miRNAs in blood samples from hundreds of individuals with or without pancreatic cancer, including cancer-free individuals with persistent pancreatic infections. The search led to more than three-dozen miRNAs showing expression that differed significantly between individuals with pancreatic cancer in the discovery group and unaffected individuals.

Following further testing with samples from a training cohort, the team developed two potential diagnostic panels — one based on four miRNAs and another based on 10 miRNAs.

Those panels correctly classified blood samples from individuals with pancreatic cancer in the majority of cases, often exhibiting enhanced accuracy when blood levels of the cancer antigen CA19-9 were considered as well.

Though more research is needed to verify such findings, those involved in the study are enthusiastic about the possibility of developing blood miRNA-based markers for diagnosing pancreatic cancer down the road.

"Although we validated our panels, our findings are preliminary," senior author Julia Johansen, an oncology researcher at Copenhagen University Hospital, and her colleagues wrote. "Further research is needed to understand whether these microRNAs have clinical implications as a screening test for early detection of pancreatic cancer and how much this information adds to serum CA19-9."

Despite efforts to come up with effective treatments for the disease, the prognosis for individual pancreatic cancer remains poor.

The five-year survival rate for pancreatic cancers hovers around just 6 percent, authors of the new study noted, and just 20 percent or so of those diagnosed with the disease are eligible for potentially curative surgical treatments — in part because many pancreatic tumors have already spread locally or to other parts of the body by the time they're diagnosed.

Past studies suggest that around 80 percent of individuals with pancreatic cancer have higher-than-usual levels of a cancer antigen known as CA19-9 in their bloodstream. That marker is currently used to provide prognostic clues for some individuals who are already known to have pancreatic cancer, though some have suggested that the antigen may have additional diagnostic applications.

MicroRNA markers have been proposed as well, with at least some prior research pointing to individual miRNAs or yet-to-be-validated miRNA panels that appear to have altered expression in the blood of pancreatic cancer patients.

In a gambit to come up with additional blood miRNA-based early detection methods, authors of the new study decided to profile miRNA expression patterns in individuals with pancreatic cancer, healthy counterparts from the same population, and those afflicted with other, persistent pancreatic maladies.

The team started with blood samples from 409 Danish individuals with pancreatic cancer and 25 individuals with chronic pancreatitis who had been enrolled as part of a Danish study called the Biomarkers in Patients with Pancreatic Cancer, along with samples from 312 healthy blood donors from the same population.

When they used the Taqman Human microRNA assay kit to profile expression levels for 754 miRNAs in blood samples from 143 pancreatic cancer cases, 69 healthy controls, and 18 pancreatitis cases selected for the discovery cohort, the researchers uncovered 38 miRNAs with significantly different levels in the blood of those with pancreatic cancer.

With the help of a training cohort comprised of 180 individuals with pancreatic cancer, 199 unaffected controls, and a lone individual with chronic pancreatitis, the team narrowed in on a panel of four miRNAs as well as a 10-miRNA panel that appeared to have diagnostic potential.

The researchers found that both of those miRNA panels had 85 percent specificity for detecting pancreatic cancer in the training cohort samples.

The sensitivity was slightly lower in the validation cohort — which included 86 individuals with pancreatic cancer, 44 healthy controls, and seven individuals with chronic pancreatitis — and in a sample set that contained early stage pancreatic cancers.

In at least some of the case or control groups, though, the investigators found that it could boost the tests' performance by folding in CA19-9 data. For instance, they found that the miRNA panels showed higher accuracy in the discovery and training cohort samples compared with the CA19-9 only test. On the other hand, the miRNA sets alone were less accurate than CA19-9 profiles for classifying samples from the validation set.

"Although the analyses do not show that these microRNA panels provide significant information over serum CA19-9, they raise the possibility that the indices could be useful in combination with CA19-9 or in situations in which CA19-9 is normal," Johansen and co-authors wrote.

In an accompanying editorial in JAMA, the University of Alabama at Birmingham's Donald Buchsbaum, a radiation oncology researcher, and Ohio State University Comprehensive Cancer Center researcher Carlo Croce agreed that "it is important that new diagnostic approaches, such as the one used in this study, are sought." Still, they cautioned that "additional rigorous investigations will be necessary to support and extend these interesting findings."