Preliminary research suggests that the expression pattern of microRNA (a short RNA molecule) may be useful in differentiating between chronic pancreatitis and pancreatic cancer and may be able to distinguish long and short term survival time for patients with pancreatic cancer, according to an article in the May 2 issue of JAMA.
Pancreatic cancer is a lethal disease, with the annual deaths nearly equaling the incidence of 33,000 in the United States, according to background information in the article. In humans, aberrant expression of miRNAs contributes to carcinogenesis by promoting the expression of proto-oncogenes (a normal gene that has the potential to become an oncogene [a gene that can cause a cell to become malignant]) or by inhibiting the expression of tumor suppressor genes. MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids; nucleic acids are present in all living cells). The role of miRNAs in ductal adenocarcinoma (malignant tumor) of the pancreas is not clear.
Mark Bloomston, M.D., of Ohio State University, Columbus, Ohio, and colleagues conducted a series of experiments to identify the pattern of miRNA expression in pancreatic adenocarcinoma to attempt to differentiate pancreatic cancer from benign pancreatic tissue and any differences in survival associated with certain miRNA expression. Study specimens were obtained at a National Cancer Institute–designated comprehensive cancer center from patients with ductal adenocarcinoma of the pancreas (n = 65) or chronic pancreatitis (n = 42) (January 2000-December 2005). RNA was harvested from resected pancreatic cancers and benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens and subsequent miRNA was analyzed to identify associations with certain tissue types and prognosis.
“We have identified—we believe for the first time—a global expression pattern of miRNAs that can differentiate ductal adenocarcinomas of the pancreas from normal pancreas and chronic pancreatitis with 95 percent accuracy,” the authors write. “A subgroup of 6 miRNAs was able to distinguish long-term [greater than 24 months] survivors with node-positive disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor survival (midpoint, 14.3 months vs. 26.5 months).”
“The present report contributes to the growing understanding of the role of miRNAs in oncogenesis and describes the global expression patterns of miRNAs in pancreatic adenocarcinoma. As we and other laboratories continue to identify the expression patterns of various solid tumors, the application of this knowledge may be broad. Such patterns may be able to be used to direct therapy in patients with metastatic tumors of unknown primary neoplasms or to help discriminate between benign and malignant neoplasms that would otherwise be indeterminate by routine histologic and immunohistochemical analysis.”
“More importantly, data such as ours, in which it is possible to begin to differentiate between patients with better or worse prognoses, may help guide the clinician when determining who should or should not receive aggressive therapy. Aside from these diagnostic and prognostic examples of how miRNA expression patterns can be used clinically, the ability of miRNAs to affect multiple genes in various pathways make them a logical target for investigation of novel antitumoral therapies. However, these preliminary data will first need to be validated in other studies,” the authors write.
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
JAMA EDITORIAL: TRANSLATING MICRORNA DISCOVERY INTO CLINICAL BIOMARKERS IN CANCER
In an accompanying editorial, Scott A. Waldman, M.D., Ph.D., of Thomas Jefferson University, Philadelphia, and Andre Terzic, M.D., Ph.D., of Mayo Clinic, Rochester, Minn., comment on the findings of Bloomston and colleagues.
“In the context of these exciting observations in a disease characterized by a dismal prognosis, should clinical oncologists and cancer geneticists begin to apply miRNA profiling to establish stratification of risk or define therapeutic targets in patients with pancreatic cancer? Although the analyses of Bloomston et al provide an initial glimpse into the future of clinical oncology, they reflect the beginning of the continuum integrating discovery, development, regulatory review, and the evidence basis of medicine required to translate advanced technology into clinical practice, a framework that has largely been ignored in the field of biomarkers. Indeed, while biomarkers represent the envisioned future for individualized management of patients with cancer, their potential has yet to be realized.”
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.