Scientists discover protein that could impact prostate cancer care
By Jack Mazurak
Researchers at the University of Mississippi Medical Center Cancer Institute
recently identified a protein that could help doctors give a clearer prognosis to patients with high-risk prostate cancer.
“Our goal was to identify biomarkers associated with patient survival in prostate cancer,” said Dr. Christian Gomez
, associate professor of pathology
and Cancer Institute researcher.
Biomarkers – such as genes and their product proteins – act as flags to help identify all kinds of specimens and diseases, including subtypes of cancers.
Finding new prostate cancer biomarkers ultimately could improve patient care through better diagnostic methods, predictive models and improved therapies and drugs.
“The idea is you want to be able to tell patients very quickly whether to consider a prostatectomy, to just keep up surveillance, or to go home and forget about it,” he said.
Prostate cancer, the second-leading cause of cancer deaths in the U.S.
, killed nearly 30,000 men last year, according to American Cancer Society estimates. With approximately one in every six U.S. men diagnosed with prostate cancer, and likely many more cases going undetected, medicine needs better tools.
In their research, Gomez and his collaborators at UMMC and the Mayo Clinic
figured the low-oxygen environment of prostate cancer tumors might hold clues.
Low oxygen, a condition known as hypoxia, results from tumors’ ravenous need for oxygen to support their rapid growth. They hastily build rogue blood vessel networks to feed themselves, but those inefficient networks often provide less oxygen than normal, well-built systems would.
That hypoxic environment can make gene activity go haywire. Like a set of poorly managed checkout lanes in a grocery store, production of proteins in some genes gets amped up way beyond normal, a situation know as over expression. Production in other genes slows to an indifferent shuffle.
Gomez and his team compared gene expression in 100 prostate tumor samples and 71 normal-tissue control samples to narrow a group of more than 500 candidate genes to 24 that are significantly over- or under-expressed in hypoxia. They further whittled the field by correlating the gene candidates with patient survival and Gleason score
, a standard evaluative measure in prostate cancer.
Using a Mayo Clinic database, they computer-matched 150 pairs of prostate cancer cases that had similar clinical characteristics and pathological scores, but differed in outcomes – meaning patients either survived or did not. They then tested the matched pairs for levels of proteins encoded by three candidate genes.
“We found that of the three candidates, HURP, a protein encoded by the gene DLG7, had the best predictive value for good outcomes,” Gomez said.
The journal Public Library of Science One
published his study in December.
The whole area of hypoxia-related genes could be rich ground for researchers to search for other prostate cancer biomarkers, Gomez said. As well, oxygen-sensitive genes could become a target for cancer-fighting drugs and therapies.
“I think we need to reengineer our thought processes and experiments to capture the characteristics in real, live tumors and use those to our benefit,” he said.
Since the researchers studied samples and cases from Caucasians in Minnesota, Gomez plans to test the findings in a group of African-American patients in Mississippi, a population that suffers higher death rates from cancer.
“We have a fertile landscape to develop these types of studies,” he said. “We have one of the most at-risk populations on the planet.”
If further testing proves HURP is a viable biomarker, it would give physicians another tool to predict a patient’s prognosis.
“With a tumor sample, something that’s routinely taken in prostate cancer patients, a hospital laboratory can isolate the RNA from that particular gene,” Gomez said.
He also plans to investigate other potential roles of HURP, including whether it plays a part in making tumors more resistant to chemotherapy and radiation treatments and whether it is a biomarker for colorectal cancer.