U-M scientists zero in on pancreatic cancer genes

Updated 1:00 PM June 24, 2003

U-M scientists zero in on pancreatic cancer genes

By Kara Gavin
UMHS Public Relations

Being diagnosed with pancreatic cancer is like receiving a death sentence—one that, for many patients, is carried out within weeks or months of their cancer's discovery. Fewer than 20 percent of patients are diagnosed in time to qualify for the only known cure—an arduous operation—and only 3 percent of all patients live even five years.

But a team of researchers from the U-M Comprehensive Cancer Center hopes to overturn that death sentence through studies that zero in on the genes and proteins that help pancreatic cancer grow and spread.

A detail from a graphic representation of the gene expression rates in different tissue types for the 80 most promising pancreatic cancer genes.

In a new paper in the journal Cancer Research, and through work funded by a $2.36 million grant received last month, as well as a new patient care program, the team aims to find new ways to improve diagnosis and treatment of the deadly disease.

In the paper, published May 15, the team reports finding 158 genes specific to pancreatic cancer—the most accurate list to date. Team members used tissue samples that had been processed swiftly after being removed from patients, to preserve fragile molecules that act as telltale signatures for genes that are "turned on" or expressed.

Unlike other scientists, the U-M team was able to distinguish genes involved in cancer from those involved in a chronic inflammatory disease, pancreatitis, that's often mistaken for cancer. Both diseases produce similar scar tissue around the pear-shaped pancreas gland, which produces insulin, hormones and digestive juices. The team narrowed the list of genes down to 80 that were expressed three times more often in pancreatic cancer cells than in non-cancerous or pancreatitis cells.

As a result, members of the U-M team believe their results will be more applicable to making specific diagnostic tests and effective treatments. The new paper even reports their success in identifying and detecting four of the proteins—14-3-3-sigma, S100P, S100A6, Beta-4 integrin—are encoded by the cancer-specific genes.

The new grant from the Michigan Life Sciences Corridor will let the team continue cataloging proteins associated with the genes, and determine which of them might be "biomarkers" that could be used in diagnostic tests or treatment planning.

"Pancreatic cancer is one of the swiftest and surest cancer killers, and not nearly enough has been learned about what, at the molecular level, makes it so deadly," says Craig Logsdon, lead author of the new paper and principal investigator on the new grant. "Others have made lists of genes that might be involved, but ours provides a much more accurate accounting, and reveals dozens of novel genes."

Logsdon, a professor of physiology at the Medical School, has special expertise in studying the pancreas. He co-leads the team with Dr. Diane Simeone, who removes pancreatic tumors from patients as an associate professor in the Department of Surgery's Gastrointestinal Surgery division, and directs studies of the cancer in her basic research laboratory.

The newly published paper is based on tissue from 10 pancreatic tumors, five samples from pancreatitis patients and five samples of normal pancreas, as well as seven commercially available pancreatic cancer cell lines. The researchers screened all the cell types for expression of more than 6,800 genes, and focused in on those expressed more often in cancer cells.

Late diagnosis, a lack of effective treatment options, rapid metastasis and a dearth of research on how pancreatic cancer works combine to make the nation's 10th most common cancer into its fourth most deadly cancer. More than 29,000 Americans are diagnosed with it each year, most of them already too far advanced to be treated.

Simeone and her colleagues have established a new comprehensive pancreatic cancer clinic that will give patients access to a broad range of clinical and supportive care, and help speed the clinical trials process.

Dr. Samir Hanash, professor of pediatrics and an oncology specialist, was senior author on the new paper and is an internationally recognized expert in this area. Besides Logsdon, Simeone and Hanash, the authors include surgery resident Dr. Charles Binkley; physiology research fellow Thiruvengadam Arumugam; associate pathology professor Dr. Joel Greenson; associate clinical pathology professor Dr. Thomas Giordano; and senior pediatrics research associates David Misek and Rork Kuick.

In addition to the new Life Sciences Corridor grant, the team has support from the Lustgarten Foundation for Pancreatic Cancer Research, the U-M Comprehensive Cancer Center and the National Cancer Institute. U-M has applied for a patent on the entire gene list published in Cancer Research.

U-M scientists zero in on pancreatic cancer genes

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