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MicroRNA Biomarkers Show Promise For Detecting Pancreatic Cancer

NEW YORK (GenomeWeb News) – A team of Texas researchers has published a proof-of-principle study suggesting microRNAs in the blood can be used as biomarkers for pancreatic cancer.

Researchers from the MD Anderson Cancer Center in Houston assessed the levels of four miRNAs in dozens of pancreatic adenocarcinoma patients and healthy controls. All four miRNAs were elevated — to varying degrees — in blood samples from individuals with pancreatic cancer. And together, the miRNA panel could detect more than 60 percent of the pancreatic cancer cases. The work appeared online this week in the journal Cancer Prevention Research.

"Our present findings that plasma miRNA analyses can help differentiate pancreatic adenocarcinoma patients from healthy controls now provide compelling evidence in support of miRNA profiling in blood plasma being a viable novel approach for developing a minimally invasive biomarker assay for pancreatic cancer," senior author Subrata Sen, a molecular pathology researcher at the MD Anderson, and his colleagues wrote.

Pancreatic cancer is one of the most common causes of cancer death in the US, with fewer than five percent of patients surviving five years or more after their diagnosis. But because there are no obvious symptoms associated with the early stages of pancreatic cancer, the researchers noted, pancreatic cancer typically is not diagnosed until it has already spread locally or metastasized to other parts of the body.

That has spurred the search for non-invasive markers, such as blood-based biomarkers, that can help find pancreatic cancer earlier.

For the latest paper, Sen and his colleagues attempted to find pancreatic cancer biomarkers by focusing on miRNAs — short RNAs between 18 and 24 nucleotides long. The research was supported by the National Cancer Institute's Early Detection Research Network, or EDRN.

"We were one of the laboratories which were funded [by EDRN] to be a biomarker developmental lab," Sen told GenomeWeb Daily News. "There is a major push in the biomarker research field to find biomarkers which can be assayed in the blood and body fluid."

To look for changes to miRNA changes in blood that differed in those with pancreatic cancer, the researchers obtained blood samples from 28 individuals with localized, locally advanced, or metastatic pancreatic cancer and from 19 healthy controls.

After treating the blood samples with DNAse and heparinase to remove impurities that could muddle their results, the researchers used real-time reverse transcription PCR to assess the levels of four miRNAs — miR-21, miR-210, miR-155, and miR-196a — in each of the samples.

The team selected these miRNAs based on both gene expression and miRNA studies of pancreatic cancer, Sen explained, noting that some of the miRNAs were previously found in pancreatic cancer while others are thought to regulate genes that are differentially expressed in pancreatic cancer.

Indeed, the researchers found that all four miRNAs were present at higher levels in blood samples from pancreatic cancer patients. When they looked at each miRNA individually, the team found that the miRNAs had between 42 percent and 53 percent sensitivity and 73 percent and 89 percent specificity to detect pancreatic cancer.

When the researchers considered all four miRNAs together, they found that the miRNA panel detected pancreatic cancer from blood samples with 64 percent sensitivity and 89 percent sensitivity. At 100 percent specificity, they calculated, the sensitivity of the panel in plasma would be 46 percent.

The team plans to publish additional pancreatic cancer biomarker papers in the near future, Sen noted. They are reportedly starting larger follow-up studies in collaboration with other members of the EDRN to look at the miRNA profiles associated with different pancreatic cancer stages.

In addition, Sen pointed out that he and his co-workers are in the process of expanding their biomarker search by taking a genome-wide approach to finding characteristic miRNAs in pancreatic cancer using miRNA microarrays.

"Certainly this study is going to be extended and expanded," he said. "We are extending it to make it a more global, genome-wide study."

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