MicroRNAs Circulating in Blood Show Promise as Biomarkers to Detect Pancreatic Cancer
M. D. Anderson News Release 09/04/09
A blood test for small molecules abnormally expressed in pancreatic cancer may be a promising route to early detection of the disease, researchers at The University of Texas M. D. Anderson Cancer Center report in the September edition of the journal Cancer Prevention Research.
The team's analysis of four microRNAs (miRNA) found in the blood plasma of pancreatic cancer patients is proof of principle to further develop a blood test for this evasive disease, said senior author Subrata Sen, Ph.D., associate professor in M. D. Anderson's Department of Molecular Pathology.
"Increased expression of microRNAs is known to be involved with specific genetic pathways and processes responsible for the development of cancer-associated changes in cells," Sen said. "Detection of elevated levels of miRNAs in blood plasma of pancreatic cancer patients as informative biomarkers of disease appears to be a promising, novel approach for developing a minimally invasive assay for detecting this disease."
There is no accurate, noninvasive way to detect pancreatic cancer, the fourth-leading cause of cancer-related deaths in the United States. Fewer than 5 percent of patients survive to five years.
MicroRNAs are single-stranded bits of RNA consisting of 18 to 24 nucleotides that regulate the messenger RNA (mRNA) expressed by genes to tell a cell's protein-making machinery what protein to make.
The four targeted microRNAs previously had been associated in varied ways with pancreatic cancer or with precancerous lesions. Expression of the four was analyzed in 28 patients with pancreatic cancer and 19 healthy people.
The four combined markers accurately identified 64 percent (sensitivity) of the pancreatic cancer cases and correctly identified 89 percent of those without disease (specificity). That degree of sensitivity and specificity are good for a pilot study but don't yet rise to the levels required for translation in the clinic, which would require investigating more circulating microRNAs in blood in a larger sample of persons representing different stages of the disease and healthy controls.
The study's small sample size, which compared only the extremes of pancreatic cancer or the complete absence of the disease, is a limitation, but the results justify continued development of this strategy, Sen said.
One of the miRNAs in the study is overexpressed in precursor lesions that can lead to full pancreatic cancer. "The fact that a microRNA reported to be overexpressed in pre-invasive pancreatic cancer could be detected in blood plasma from pancreatic cancer patients raises the possibility that a blood test for detecting pre-invasive pancreatic cancer may become a reality," Sen said.
Marker miRNAs used in the study were miR-21, miR-210, miR-155 and miR-196a.
Sen and colleagues are working with the Early Detection Research Network of the National Cancer Institute to develop studies with larger sample sizes that are designed to test miRNA markers associated with different grades and stages of the disease.
The project was funded by grants from the National Cancer Institute.
Co-authors with Sen are first author Jin Wang, Ph.D., and Aimee LeBlanc, BS, also of Molecular Pathology; Jinyun Chen, Ph.D. and Marsha Frazier, Ph.D., of M. D. Anderson's Department of Epidemiology; Ping Chang, Donghui Li, Ph.D., and James Abbruzzese, M.D., all of the Department of Gastrointestinal Medical Oncology; and Ann Killary, Ph.D., of the Department of Genetics. 09/04/09