New Test for Pancreatic Cancer Based on MicroRNAs in Blood

Zosia Chustecka

January 21, 2014

A new test for pancreatic cancer based on detecting microRNAs in whole blood is described by researchers from Denmark in the January 22/29 issue of JAMA.

The team, led by Nicolai Schultz, MD, PhD, from Herlev Hospital, Copenhagen University Hospital, developed 2 novel panels of microRNAs, which are small noncoding single-stranded RNAs (about 18 to 24 nucleotides) that act on target genes at the messenger RNA level to promote oncogenesis.

The team tested the panels in a series of studies involving a total of 409 patients with pancreatic cancer, 25 patients with pancreatitis, and 312 healthy control subjects.

The panels were tested alone and also in combination with the serum marker CA19-9, which is already approved for prognosis determination, and as a guide to treatment and follow-up in patients with pancreatic cancer (although it is not approved for diagnosis).

"Pancreatic cancer is a very lethal disease, and today most patients are diagnosed too late for surgery to be performed," the researchers comment.

They suggest that using their microRNA tests in combination with serum CA19-9 for screening patients with symptoms could identify the disease at an earlier stage, and "thus could have potential to increase the number of patients that can be operated on and possibly cured of pancreatic cancer."

However, the researchers caution that their findings are preliminary.

Two experts writing in an accompanying editorial concur. "Additional rigorous investigation will be necessary to support and extend these interesting findings," write Donald Buchsbaum, PhD, from the University of Alabama at Birmingham, and Carlo Croce, MD, from the Ohio State University in Columbus.

Two Panels Developed

The Danish researchers developed 2 novel panels of microRNAs for diagnosing pancreatic cancer: index I containing 4 microRNAs, and index II containing 10.

Both of these diagnostic indices performed better than serum CA19-9 in the discovery cohort (comprised of 143 patients with pancreatic cancer, 18 patients with chronic pancreatitis, and 69 healthy control subjects).

In addition, index II also performed better than CA19-9 in the training cohort (180 patients with pancreatic cancer and 199 healthy control subjects).

However, CA19-9 performed better than both indices when used alone in the validation cohort (86 patients with pancreatic cancer, 7 patients with chronic pancreatitis, and 44 healthy participants).

Importantly, in all 3 cohorts, the combination of CA19-9 with either index performed better than serum CA19-9 alone (as measured by area under the curve [AUC]).

Despite the modest improvement in AUC, these data do not demonstrate that the microRNA signatures provided clinically significant information over serum CA19-9, the editorialists comment.

Even though the study was relatively large, well-conducted, and addressed an important topic, the authors "appropriately acknowledge the exploratory nature of the investigation," Dr. Buchsbaum and Dr. Croce comment.

"Further research is necessary to understand whether the microRNA signatures have clinical implications for the early detection of pancreatic cancer and whether this information adds substantially to serum CA19-9," they conclude.

The study was supported by research grants from Herlev Hospital; the Danish Ministry of Science, Technology and Innovation; the Danish Cancer Society; and several others. Dr. Schultz and 3 coauthors report that they are all named in a European patent application submitted by Copenhagen University Hospital. Dr. Buchsbaum and Dr. Croce have disclosed no relevant financial relationships.

JAMA. 2014; 311, 392-404, 363-365. Abstract, Editorial

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