Molecular Marker Appears to Detect Pancreatic Cancer

A very big cancer breakthrough pending (not just for pancreatic cancer)

May 1, 2007 — A new study shows that microRNA can identify lethal pancreatic cancer and may even be able to predict long- and short-term survival. The promising marker, described in the May 2, 2007 issue of the Journal of the American Medical Association, appears to differentiate between a healthy pancreas, cases of chronic pancreatitis, and cancer. In an accompanying editorial, the authors call the analyses "an initial glimpse into the future of clinical oncology."

Editorialists Scott Waldman, MD, from Thomas Jefferson University, in Philadelphia, Pennsylvania, and Andre Terzic, MD, from the Mayo Clinic in Rochester, Minnesota, say the field of clinical oncology is poised for unprecedented innovation. They predict breakthroughs in decoding disease pathobiology. "Harnessing the full potential of transformative advances is predicated on defining biomarkers that promote targeted cancer prevention, diagnosis, and treatment of individual patients and populations," they write.

But, the doctors caution, "while biomarkers represent the envisioned future for individualized management of patients with cancer, their potential has yet to be realized."

During an interview with Medscape, lead author Mark Bloomston, MD, from the James Cancer Hospital and Solove Research Institute, Ohio State University, in Columbus, said he agrees. "This is just the first step of many in identifying microRNA as a tool to help with diagnosing disease, predicting outcome, and possibly in the future, of developing into a potential treatment." Dr. Bloomston says genetic research is gaining momentum and represents an important new frontier in managing disease.

MicroRNAs are small noncoding ribonucleic acids. Abnormal expression of microRNA is said to contribute to carcinogenesis by promoting the expression of protooncogenes or by inhibiting the expression of tumor-suppressor genes. The role of microRNA in ductal adenocarcinoma of the pancreas remains unclear.

Identified Pancreatic Cancer from Healthy Controls in 90% of Cases

"In this report," the investigators write, "we describe a series of experiments designed to identify the global pattern of microRNA expression in pancreatic adenocarcinoma to accomplish several goals. First, we sought to define microRNAs that can differentiate pancreatic cancer from benign pancreatic tissue. Since pancreatic cancer often occurs in a background of chronic pancreatitis, we also used chronic-pancreatitis specimens as a second control." Next, they note, "we hypothesized that a separate pattern of microRNA expression could distinguish patients more likely to achieve long-term survival from those with shorter survival. Finally, we hoped to identify microRNA with expression predictive of survival."

Dr. Bloomston and his team obtained study specimens from a National Cancer Institute–designated comprehensive cancer center from patients with ductal adenocarcinoma of the pancreas (n=65) or chronic pancreatitis (n= 42). They harvested RNA from resected pancreatic cancers and benign adjacent pancreatic tissue as well as from chronic pancreatitis specimens.

The researchers were able to distinguish pancreatic cancer from normal pancreas in 90% of cases and, separately, from chronic pancreatitis in 93% of cases. A subset of microRNAs was of prognostic value identifying patients with pancreatic cancer who survived longer than 24 months compared with those who survived less. In addition, the expression of 1 specific species of microRNA predicted overall poor survival (median 14.3 months) compared with patients whose tumors did not express this species (median 26.5 months).

"These results highlight the potential of microRNA profiling for defining prognosis and risk stratification, identifying low- and high-risk populations of patients with pancreatic cancer," the editorialists write. "Moreover, the findings underscore the potential value of microRNAs as mechanism-based therapeutic targets in cancer, certainly a critical unmet clinical need in the management of pancreatic cancer."

Relationships defining the clinical usefulness of a biomarker should be assessed in randomized clinical trials and subsequently validated in follow-up trials, they add.

"Another group from our campus conducting comparable work has seen similar results," Dr. Bloomston told Medscape. "Although it is still early, we are already seeing some validation of our work, and I think it's fair to say that microRNA will likely have an important role moving forward."

JAMA. 2007;297:1901-1908, 1923-1925.

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