MicroRNAs in Blood May be Biomarkers of Pancreatic Cancer
Small molecules known as microRNAs, which can be detected in blood samples, have the potential to help identify patients with pancreatic cancer, a study finds. The study, by researchers at The University of Texas M.D. Anderson Cancer Center in Houston, was supported by the Early Detection Research Network (EDRN) of the National Cancer Institute (NCI), part of the National Institutes of Health. The paper appeared online Sept. 1, 2009, in Cancer Prevention Research.
Pancreatic cancer is a highly fatal disease that is difficult to detect at early stages. In most patients, symptoms do not appear until the cancer is locally advanced or has spread to other parts of the body. The absence of symptoms in early-stage disease and the current lack of effective, minimally invasive screening and diagnostic techniques limit the available treatment options. Both contribute to the high mortality rate observed for patients with pancreatic cancer.
"The development of a minimally invasive test for the early detection and diagnosis of pancreatic cancer is greatly needed," said Sudhir Srivastava, Ph.D., chief of the Cancer Biomarkers Research Group in NCI's Division of Cancer Prevention. "An important step is to identify biomarkers for pancreatic cancer, such as microRNAs, circulating in the bloodstream that can be used to distinguish individuals with pancreatic cancer from individuals without the disease."
MicroRNAs, or miRNAs, are short strands of RNA. The miRNAs regulate gene expression by controlling the translation of a specific type of RNA called messenger RNA which relays the genetic instructions for making proteins. Previous research has indicated that miRNAs play important roles in regulating normal cell proliferation and in cancer. Altered patterns of miRNA expression have been seen in pancreatic cancer as well as many other cancers. In addition, it has recently been reported that tumor-derived miRNAs can be detected in blood and that these molecules are stable in stored samples.
Thus, miRNAs circulating in the blood may have the potential to serve as novel biomarkers for the detection and diagnosis of pancreatic cancer.
To evaluate the feasibility of using miRNAs in the blood as biomarkers for pancreatic cancer, the researchers selected a set of four miRNAs that have been associated with pancreatic cancer -- miR-21, miR-210, miR-155, and miR-196a. Among these, miR-155 has been identified as a candidate biomarker for early pancreatic cancer, and expression of miR196a has been shown to increase during disease progression. Levels of all four miRNAs were assessed in blood samples from 28 pancreatic cancer patients and 19 healthy volunteers. The study population consisted of patients with pathologically confirmed pancreatic cancer and healthy disease free individuals recruited at the M.D. Anderson Cancer Center between 2002 and 2008. The team found that sensitivity -- or ability to accurately detect pancreatic cancer -- using the panel of four miRNAs was 64 percent. The panel also showed an 89 percent specificity, which indicates the proportion of study participants who did not have pancreatic cancer and were correctly identified as being disease free.
"Our results demonstrate proof of principle in developing a blood test based on miRNA signatures for pancreatic cancer," said senior author Subrata Sen, Ph.D., of M.D. Anderson's Department of Molecular Pathology. "More work is needed to evaluate this strategy in different grades and stages of the disease. We are in the process of initiating such studies in collaboration with members of EDRN." For example, the researchers will test the ability of the miRNAs to detect pancreatic cancer in separate patient populations.
Pancreatic cancer, the fourth most common cause of cancer death in the United States, has a poor survival rate compared with that of other types of cancer. Less than five percent of the patients with pancreatic cancer survive five years past diagnosis.
For more information about the Department of Molecular Pathology at M.D. Anderson, please go to http://www.mdanderson.org/education-and-research/departments-programs-and-labs/departments-and-divisions/molecular-pathology/index.html.
For more information on NCI's EDRN, please go to: http://edrn.nci.nih.gov.
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Reference: Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, and Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood based biomarkers of disease. Cancer Prevention Research. Online September 1, 2009.