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NYU/Exiqon Team Finds New Blood-Based miRNA Markers for Melanoma Recurrence


This article has been updated from a version posted June 16 to note that the miRNAs identified in the study require validation.

By Molika Ashford

Researchers from New York University, working with diagnostic company Exiqon, have identified several blood-based microRNAs with the potential to be used as biomarkers for melanoma recurrence risk.

They shared their results in a poster at the annual meeting of the American Society of Clinical Oncology earlier this month.

According to the poster, adding a recurrence signature based on serum miRNAs found in the study to standard clinical examination methods improved prognostic performance significantly — from an area under the curve of 0.64 to an AUC of 0.93.

Exiqon, which provided the array platform used for the miRNA discoveries, plans to work with the NYU team to validate the results with the eventual goal of creating a clinical prognostic test.

"The point is not to develop something very difficult" to use, Iman Osman, a professor at the NYU Langone Medical Center and an author of the ASCO poster, told Gene Silencing News this week. "You need to have something simple...but simple, reproducible, sensitive and specific."

"Basically we wanted to know, 'Can we have markers at the time of diagnosis that can better predict the outcomes of these patients,'" she said.

According to Osman, blood-based microRNAs could give clinicians the opportunity to monitor a patient over time. "You cannot take a biopsy every three months," she said. "But you can get blood from the patient every three months."

Melanoma, meanwhile, has been rising in incidence, doubling in the last decade, according to Osman. The standard-of-care clinical staging system for tumors, used at the time of diagnosis, leaves much to be desired in terms of prognostic precision, she said. Because of this, the possibility of using miRNAs is attractive.

Basing a patient's chances of survival or recurrence on a staging system is far from ideal, she said. "Telling patients, 'You have 90 percent chance,' is great, but you don't know if this patient will land in the 90 percent or the 10 percent. And if you have stage three, actually it becomes more complex because you are telling patients it's 50/50. That doesn't help you, it's more like pure chance," she said.

"So we [wanted to] develop a new [prognostic] assay that can better define the chance of recurrence or survival."

To identify miRNAs that would serve as markers for melanoma recurrence risk, the researchers combined a "discovery approach," using an Exiqon array to examine the full spectrum of miRNA present in blood, and a targeted approach to quantify 18 miRNAs already identified as likely candidates.

Using both approaches was "unique," Osman said. "We said we will not compromise the advantages of both methods."

The researchers looked at blood samples from 146 melanoma patients from a prospective database at the school's medical center, using Exiqon's LNA Universal RT microRNA PCR system to examine 81 of the original 146 in their discovery approach. They also examined 55 control samples divided between healthy volunteers, rheumatoid arthritis sufferers, and patients with bladder and renal cancers.

A recurrence signature of five miRNAs identified by the Exiqon array raised prognostic precision when added to standard clinical variables, from an AUC of 0.64 to 0.93. Four of the five — miR-222, miR-182, miR-339-3p, and miR-338-3p — were statistically significant predictors of melanoma recurrence.

Exiqon and Osman stressed that the work still requires validation and the miRNAs identified in the study are not definitive.

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Only miR-222 and miR-182 were identified as predictive of recurrence using both the targeted approach and the discovery approach, but "the fact that there were some picked up by one and not another meant that both were useful and if you focus on one but not the other you are missing part of the picture," Osman said.

Now the researchers plan to do validation studies looking at both groups of biomarkers.

Osman said she is currently studying a small validation set of 60 or 70 samples, and is applying to the National Cancer Institute's clinical assay development program for help getting access to a larger validation cohort of 3,000 samples.

The NYU group's relationship to Exiqon is still new, according to both Osman and Adam Baker, Exiqon's vice president of diagnostics & pharmaceutical alliances. Osman said that working with the company will help eventually move this research toward development as a commercial assay.

"We need to develop a kit, and this is beyond what we would do as academics," she said.

"They will bring the samples, and together we're finding new samples – we bring the technology platform, and we're working with it always with the sense of how can we get this platform into a clinical setting to commercialize it," said Baker. "Together we can go out to look for other partners to really commercialize it later on."

Baker noted that the research is still at too early a stage to have a timeline for commercialization, however.

"It is progressing rapidly, though," he said. "These blood-based tests… in this area where there are currently not many options, have a real chance of moving quickly into clinical testing labs."

Have topics you'd like to see covered in Gene Silencing News? Contact the editor at mashford [at] genomeweb [.] com.